Document Detail

Gut-central nervous system axis is a target for nutritional therapies.
Jump to Full Text
MedLine Citation:
PMID:  22490672     Owner:  NLM     Status:  MEDLINE    
Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.
Gustavo D Pimentel; Thayana O Micheletti; Fernanda Pace; José C Rosa; Ronaldo V T Santos; Fabio S Lira
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-04-10
Journal Detail:
Title:  Nutrition journal     Volume:  11     ISSN:  1475-2891     ISO Abbreviation:  Nutr J     Publication Date:  2012  
Date Detail:
Created Date:  2012-05-04     Completed Date:  2012-08-23     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101152213     Medline TA:  Nutr J     Country:  England    
Other Details:
Languages:  eng     Pagination:  22     Citation Subset:  IM    
Department of Internal Medicine, State University of Campinas, Campinas, Brazil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Appetite Regulation
Bariatric Surgery
Central Nervous System / metabolism*,  microbiology
Diabetes Mellitus, Type 2 / diet therapy*
Gastrointestinal Hormones / metabolism
Gastrointestinal Tract / metabolism*,  microbiology
Inflammatory Bowel Diseases / diet therapy*
Obesity / diet therapy*
Postprandial Period
Reg. No./Substance:
0/Gastrointestinal Hormones

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Nutr J
Journal ID (iso-abbrev): Nutr J
ISSN: 1475-2891
Publisher: BioMed Central
Article Information
Download PDF
Copyright ©2012 Pimentel et al; licensee BioMed Central Ltd.
Received Day: 19 Month: 8 Year: 2011
Accepted Day: 10 Month: 4 Year: 2012
collection publication date: Year: 2012
Electronic publication date: Day: 10 Month: 4 Year: 2012
Volume: 11First Page: 22 Last Page: 22
ID: 3342925
Publisher Id: 1475-2891-11-22
PubMed Id: 22490672
DOI: 10.1186/1475-2891-11-22

Gut-central nervous system axis is a target for nutritional therapies
Gustavo D Pimentel16 Email:
Thayana O Micheletti2 Email:
Fernanda Pace1 Email:
José C Rosa3 Email:
Ronaldo VT Santos4 Email:
Fabio S Lira5 Email:
1Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil
2Faculty of Applied Science, State University of Campinas (UNICAMP), Limeira, SP, Brazil
3Department of Physiology and Biophysics, Institute of Biomedical Sciences I, University of São Paulo (USP), São Paulo, SP, Brazil
4Department of Psychobiology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil
5Laboratory of Exercise Biochemistry and Physiology, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
6José Caetano de Lima, 682. Bairro Junqueira, Lins MA: 16403-162, SP, Brazil


The energy balance is determined by the relationship between the acquisition and expenditure of energy. This perfect interaction occurs among physiological signals in peripheral organs and the central nervous system (CNS). Apart from the obvious digestive and absorptive functions of the gastrointestinal tract, gut and adipose tissue hormones play an important role in controlling the energy balance, particularly via the regulation of food intake in both the short- and long-term, respectively. Therefore, the enteric nervous system (ENS), gut hormones, and nutrients act in the control process at the beginning and termination of meals [1,2].

The CNS-gut axis is controlled by the ENS and its importance in the health and disease has been recognised by several studies [3,4]. According to health professionals, advances in the physiological and molecular mechanisms involving the ENS are responsible for the control of the energy balance, and for the nutritional therapies used in patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases (IBDs), bariatric surgery and cancer-associated anorexia [5-9].

In the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity [10]. At this time, with the advent of studies involving the mechanisms that modulate appetite control, it was recognised that the hypothalamus is the "appetite centre". In rats, some researchers observed that lesions in the lateral hypothalamus produced anorexia (hunger centre) and lesions in the ventromedial nuclei of the hypothalamus produced obesity (satiety centre) [11-14].

More recently, the discovery of cloned leptin in 1994, which is produced and secreted by adipose tissue, provided some evidence that appetite control could also be modulated by peripheral tissues [15].

In relation to the mechanisms of intestinal hormonal action, the beginning of the food intake process results in the release of anorexigenic hormones, such as peptide YY (PYY), the glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), the glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK) and prouroguanylin (Figure 1). Likewise, the CNS receives and integrates several factors, adjusting the energy balance in accordance with energetic necessity. Overall, the secretion of anorexigenic hormones (including PYY, GLP-1, OXM, GIP, CCK and prouroguanylin) and the activation of neuropeptides, such as POMC and CART, occurs in the postprandial state. On the other hand, the greater release of the orexigenic hormone ghrelin and the activation of the neuropeptides AgRP and NPY occurs in the fasting state [16-18] (Figure 1). In the next step, the main gut hormones that influence energy homeostasis are summarised (Table 1).

For nutrition professionals, the gut-CNS axis is considered an attractive opportunity, because foods may help to treat and prevent diseases. In this review, we discuss the fact that nutritional therapies could modify the gut flora and may reach the CNS in order to modulate the food intake and inflammatory processes. Some nutritional therapies that are known to modulate the gut-CNS axis via physiological and molecular mechanisms are also discussed.

The main underlying mechanisms behind the connection between microbiota and the central nervous system

The components that interact to form this complex brain-gut communication is bidirectional, with stimuli from gastrointestinal tract (GIT) that influences the brain functions and messages from the brain that may alter some GIT activities, such as motor, sensory and secretory [19]. It was demonstrated that this link occurs via the vagus nerve to the brainstem, and via spinal afferents to the spinal cord [20]. Recently, Bravo et al. [21] showed that vagotomized mice did not exhibit behavioral and neurochemical effects that L.rhamnosus exerts in CNS, evidencing the correlation of the vagus nerve in the direct communication between the bacteria and the brain.

Moreover, the serotonin (5-HT) levels and hypothalamic-pituitary-adrenal (HPA) axis may also participate in this connection. All connections are involved with modulation of infections and inflammatory diseases, such as obesity, type 2 diabetes mellitus, ulcerative colitis, Crohn's disease, as well as with behavioural problems and psychiatric disorders, such as cognition, mood, emotion, stress and anxiety [21,22].

Diets and microbiota: A general overview

The microbes that reside in the gut favors the harvest of energy from food, influence the metabolic profiling of organs and exerts nutritional and protective effects on the intestinal epithelium and immune system [23-25]. Moreover, the microbiota consists mainly of bacteria that are divided in two main phylotypes: Bacteroidetes and Firmicutes [26,27].

Supporting normal digestion and host metabolism, gut microbiota is able to expand nutrient availability, releasing energy through fermentation of otherwise non-digestible oligosaccharides or by modulating absorption. The short chain fatty acids (SCFA), which are the major metabolic products of anaerobic bacteria fermentation, are an important energy source for humans, being used by colonocytes, liver and muscle. It has been reported that 5 to 10% of human basal energy requirements are provided by SCFA [28-31].

Since the interactions of microbes with host leads to a complex balance of host genes, alteration of microbiota population can cause several metabolic disorders.

Recently, Cryan & O'Mahony [19] suggested that numerous conditions may modify the microbiota, such as obesity, IBDs, antibiotics, infections and diets [22,32]. Therefore, the roles of the gut-CNS axis on metabolic diseases, focusing on the physiological and nutritional aspects are summarised in the Figure 2.

Obesity and type 2 diabetes mellitus

Since it is known that the microbiota is related to energy homeostasis, digestion of nutrients and metabolism, some low-grade inflammation-related diseases have emerged as an attractive opportunity for researchers.

The first studies to observe that obese microbiota have an enhanced ability to absorb energy from the diet were described by Jeffrey Gordon's group [33,34].

Cani et al. [35] proposed that both obesity and type 2 diabetes mellitus can be characterised by increased lipopolysaccharide (LPS) levels. For instance, in the presence of diet induced obesity (DIO), the LPS concentrations are higher than in the fasting state. In addition, either DIO animals or those submitted to subcutaneous injections of LPS represent enhanced LPS-containing microbiota, as well as glucose and body weight gain. Likewise, these authors were the first to demonstrate that "metabolic endotoxaemia" initiates obesity [35].

Recently, it has been shown that food rich in saturated or trans-fatty acids stimulates inflammatory markers [9,36-40]. Raybould [41] suggests that intestinal inflammation is associated with obesity due to high LPS levels. In 2011, it was shown that the ingestion of trans fatty acids during gestation and lactation led to an increase in blood LPS levels, the activation of inflammatory signalling in the hypothalamus and an increased food intake in adult offspring rats [9]. Moreover, the same studies [27,42] observed the presence of intestinal inflammation in different models of obesity, such as eating a high-fat diet, rich in saturated fatty acids and genetic obesity.

When evaluating inflammatory markers in CONV mice fed with a high-fat diet, Ding et al. [43] observed increased body weights and activation of gut TNF-α mRNA expression. Likewise, Caricilli et al. [27] showed increased blood LPS levels in toll-like receptor 2 (TLR2)-deficient mice when compared to wild-type mice. TLR2 deficient mice showed activated phosphorylation of janus kinase (JNK), TLR4 and phosphorylation in serine of the insulin receptor substrate-1 of several tissues [27]. In this work, the authors suggest that an increase in LPS levels together with TLR4, in the absence of changes of TLR2, result in a compensatory action that may lead to increased activation of TLR4. Together, this would contribute to insulin resistance in TLR2-deficient mice [27]. Likewise, in a previous study [9] performed with adult offspring rats from mothers fed trans fatty acids during gestation and lactation, increased blood LPS levels and hypothalamic TLR4 expression were seen with no change to hypothalamic TLR2 expression. Moreover, the increase of blood LPS provoked by a high-fat diet has also been shown by other recent studies [44,45]. It has also been shown that the actions of fatty acids are aggravated by physiological ligands of G-protein-coupled receptors, such as GPR40, 41, 43, 84 and 119, and, therefore, it may be involved in the progression of several inflammatory diseases [46].

Another TLR described to influence microbiota is TLR5. Vijay-Kumar et al. [47] demonstrated that mice deficient in TLR5 exhibit obesity, hyperphagia, dyslipidaemia, hypertension and insulin resistance, and that they also show an altered composition of gut microbiota, such as increased Firmicutes (54%) and lower Bacteroidetes (39.8%).

In addition to inflammatory processes, non-alcoholic fatty liver disease (NAFLD) is a typical hepatic manifestation that has been found to be obesity-related. Recently, inflammasome-deficient mice were shown to have modifications of gut microbes population through the influx of TLR4 and TLR9 agonists into the portal circulation. Therefore, increased hepatic inflammation levels can lead to the development of NAFLD and obesity [48].

An important study that demonstrated the relationship between intestinal bacterial and obesity in humans was published by Wu et al. in 2011 [49]. In this study, it was found that an increased fat intake and low dietary fibre are associated with the modulation of intestinal microbiota. The authors of this study showed that animal proteins and saturated fatty acids are associated with increased Bacteroidetes levels, and that diets containing carbohydrates but lacking meat and dairy products increased Prevotella levels. Together, these facts create a profile of weight gain and gut inflammation-related bacteria.

DIO experimental models also indicate low expression of tight junction proteins in the gut, and the increasing in intestinal permeability [41]. Brun et al. [50] found in either ob/ob and db/db mice, an alteration in the intestinal permeability same when mice were submitted to standard chow consumption. In rats fed with hyper-lipidic diet also was observed an increase of intestinal permeability through the reduction of tight junction proteins, such as claudin 1, claudin 3 and junctional adhesion molecule-1 [51].

Collectively, several obesity models have observed that a major determinant of intestinal permeability is the intercellular tight junction proteins. Tight junctions are organised by the same transmembrane proteins, such as occludin, claudin and junctional adhesion molecule-1 [52-54]. Therefore, these transmembrane proteins interact with Zonula Occludens (ZO-1-3), which anchors the transmembrane proteins [55] provoking an increase of intestinal permeability. The increased intestinal permeability is thought to be associated with a higher activity of pathogenic bacteria and inflammatory processes. In summary, some studies have described that the main tight junction proteins responsible for this intestinal permeability are ZO-1, myosin light chain, occludin, claudin and junctional adhesion molecule 1 [44,50,52-54,56,57].

Several papers suggest that saturated fatty acids might enhance the blood LPS levels through GPRs, possibly secreted by gut cells, may affect the CNS and alter numerous central inflammatory markers. In addition, the increased intestinal permeability aggravated by a high-fat diet and LPS may also be responsible for altered epithelial barrier function, and it is therefore possible that the high prevalence of obesity and type 2 diabetes mellitus is connected with an altered gut microbiota-CNS axis.

Bariatric surgery

In the middle of the 1950s, Kremen et al. [58] postulated that bypass surgery in dogs reduced food absorption. Recently, in humans, bariatric surgery has been found to be a procedure which results in patients rapidly losing weight, accompanied by the resolution of type 2 diabetes mellitus and a reduction of cardiovascular deaths [45,59]. However, the mechanisms underlying the improvement of metabolic parameters have not been fully elucidated. Likewise, Evans et al. [60] have shown that obese patients had an increase of blood PYY levels and GLP-1 was restored to normality after gastric bypass surgery compared to patients with normal weights. Short-term Rouxen-Y gastric bypass (six months) was able to activate PYY and GLP-1 secretion, and stimulated the satiety in response to a liquid-meal intake in normal, glucose-tolerant obese patients [61]. Falkén et al. [62] reported that patients had a progressive rise of the GLP-1 and OXM concentrations after gastric bypass and that this procedure favours weight loss and improved insulin sensitivity.

Collectively, the published data has shown that, after bariatric surgery, numerous gut hormones can reduce the appetite and normalise glucose homeostasis, and that the main actions are modulated through GLP-1, PYY, OXM, ghrelin, insulin and leptin [63]. Moreover, an increased secretion of anorexigenic hormones, such as GLP-1 and PYY occurs with bariatric surgery (Figure 3). It is also possible to speculate that the bariatric surgery might modulate the intestinal permeability and enhancement of anorexigenic gut hormone secretion, alongside the reduction of inflammation seen in obese patients, but this has not been evaluated. Collectively, it is known that theses anorexigenic hormones might activate POMC and CART neuropeptides in order to reduce the food intake and body weight, and also help to moderate energy expenditure.

Inflammatory bowel diseases (IBDs)

The IBDs, that affect the health of humans, include ulcerative colitis, Crohn's disease and irritable bowel syndrome (IBS) [64-66]. Macfarlane et al. [67] have suggested that the appearance of these diseases may be due to modified gut microbiota, or as a consequence of local inflammation. However, a recent study has shown that the intestinal wall of either inflamed or non-inflamed guts [68] may be associated with severe disease. Likewise, human studies of patients diagnosed with IBDs have observed increased TLR2, TLR4 and TLR5 expression in the gut wall [69,70], and other studies have reported an increase of the IL-6, IL-8, TNF-α and interferon-gamma levels [71-73]. Therefore, it is possible to observe that in IBDs that have an inflammatory status higher than that of obesity, more severe disease symptoms are seen. In order to investigate the effects of neuro-inflammation in animals submitted to experimental IBD, Wang K, et al. [74] observed increased IL-6 mRNA expression in both the colon and brain of these animals when compared to control animals.

Collectively, it can be speculated that higher levels of gut-related inflammation lead to a reduction of food intake and malnutrition due to the activation of cytokines in the CNS. According to Pavlov & Tracey [75], the autonomic nervous system plays a key role in the control of the brain in moderating the immune system and inflammation.

In summary, several studies have reported that inflammatory bowel problems are linked to a reduction of Lactobacillus spp and Bacteroidetes, and an increase of the Firmicutes-Bacteroidetes ratio [76-79]. These changes in intestinal flora are aggravated through alterations in the immune system that underlie disease pathogenesis.

Nutritional therapies that improve metabolic diseases through the gut-CNS axis

While microbes have been used to study the underlying mechanisms of inflammatory diseases and insulin resistance, numerous researchers have also stated that nutritional components could be used as a strategy to combat the gravity of these abnormalities. Historically, the Greek physician Hippocrates, "The father of medicine", reportedly said "Let your food be your medicine, and your medicine be your food".

Among the nutritional components that support a healthy intestinal microbiota, we highlight the dietary fibres, probiotics and prebiotics [80-84]. The improvements include a reduction of systemic and local inflammation, as well as less intestinal pain and discomfort, when both probiotics and prebiotics are used [80,85,86]. In addition, other studies have shown an inhibition of bacterial translocation and a reduction of intestinal permeability with the use of these nutrients [87,88].

One study demonstrated that the use of oligofructose, a prebiotic, enhanced the levels of Bifidobacterium spp., and improved insulin sensitivity, as well as restoring inflammatory status through decreased endotoxaemia metabolism [80].

Oligofructose and resistant starches have been demonstrated to increase short-chain fatty acid-induced GLP-1 expression [89], and to reduce ghrelin expression [90]. Moreover, in a recent review the nutrients and diets that stimulate the anorexigenic gut peptides, reduce the food intake and break off the obesity were summarised. The main nutrients and diets that can increase the GLP-1, CCK, GIP, OXM and PYY secretion are dietary fibre, dairy products, unsaturated fatty acids and a normal calorie diet [2].

Recently, it was observed that a prebiotic-enriched diet reduced Firmicutes and increased Bacteroidetes levels, as well as improving glucose sensitivity, body fat, inflammation and oxidative stress [91]. Furthermore, a recent review suggested that SCFA providers provided of dietary fibers, such as propionate and butyrate, induce the reduction of food intake by increasing leptin secretion and reducing pro-inflammatory cytokine expression [92]. These dietary fibres are fermented by microbiota, and higher butyric acid levels were found in animals fed with diets containing a mixture of oligofructose and raffinose [93].

Necrotising pancreatitis patients with diarrhoea received semi-elemental nutrients via jejunal feeding, and an increase in faecal short-chain fatty acids, such as acetate, propionate and butyrate were found when compared to pre-treatment levels. In addition, a resolution of diarrhoea episodes was seen in approximately 66% of patients. Therefore, this study suggests that dietary fibre supplementation is an excellent method for the improvement of healthy intestinal microbiota, and results in reduced symptoms of dysbiosis [81].

Concomitant to numerous "healthy" nutrients, it is possible that unsaturated fatty acids, such as omega-3, are an attractive option for the improvement of inflammatory processes, and that this can be modulated by the physiological ligand of these fatty acids, GPR120 [94,95].

In relation to high-grade inflammatory diseases, such as a provoked by Human Immunodeficiency Virus type1 (HIV-1), patients were shown to have infections in lymphoid tissue, alterations of intestinal microbiota and impaired symptoms of Acquired Immunodeficiency Syndrome (AIDS). Therefore, the use of probiotic diets is suggested for the prevention of progression of HIV-linked infections [96].

It has been recognised that obese, insulin-resistant and IBD subjects represent a group requiring moderation of intestinal microbiota due to a higher risk of the development of cancer. This is because the mechanisms by which intestinal bacteria induce carcinogenesis are thought to be via chronic inflammation, immune system evasion and immunosuppression. Conversely, the probiotics used have also emerged as an possible mechanism for the reduction of the pro-inflammatory status seen in cancer patients [97].

Collectively, this topic has summarised the main physiological and metabolic alterations that modify illnesses of the gut both before and after nutritional therapy (Figure 4).

Although nutritional compounds are important for the improvement of health, changes to diets, such as an increase of either fruit or vegetable consumption, as well as a reduction of refined carbohydrates and saturated and trans-fatty acids [98,99], are required, as food restriction can prevent obesity in humans [98,99] and mice deficient in the TLR5 [47]. Furthermore, micronutrients and macronutrients from existing diets are targets for gut health and strengthening of the immune system [100].

The studies discussed in this review collectively support the emerging view that microbiota contribute to metabolic disease, and suggest that an impaired diet quality may promote the development of inflammatory diseases. However, some nutrients that have been studied, such as dietary fibres, and probiotic and prebiotic nutrients, along with bariatric surgery, are one possible option for the maintenance of intestinal health, and the improvement of the gut-CNS axis (Figure 5).

In summary, the discoveries in understanding these foods and nutrients could help to regulate the gut-CNS axis, but remain a challenge for nutritionists and scientific investigators. Therefore, future research must be focused on looking to improve the effectiveness of diets for the prevention of inflammation between the gut-CNS axis, as well as for the maintenance of microbial homeostasis of the gut.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

GDP performed the design of the study, researched and discussed the articles and written the paper. TOM, FP, JCR, RVTS and FSL also researched and discussed the papers. All authors read and approved the final version manuscript.


This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

Pimentel GD MJ,Mota JF,Oyama LM,Oxintomodulina e obesidadeRev NutrYear: 20092272773710.1590/S1415-52732009000500013
Pimentel GD,Zemdegs JC,[Foods and nutrients modulates the release of anorexigenic gastrointestinal hormones]Acta Med PortYear: 20102389190021144331
Mayer EA,Gut feelings: the emerging biology of gut-brain communicationNat Rev NeurosciYear: 20111245346621750565
Washington MC,Raboin SJ,Thompson W,Larsen CJ,Sayegh AI,Exenatide reduces food intake and activates the enteric nervous system of the gastrointestinal tract and the dorsal vagal complex of the hindbrain in the rat by a GLP-1 receptorBrain ResYear: 2010134412413320452329
Inui A,Asakawa A,Bowers CY,Mantovani G,Laviano A,Meguid MM,Fujimiya M,Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organFASEB JYear: 20041843945610.1096/fj.03-0641rev15003990
Hobson KG,Havel PJ,McMurtry AL,Lawless MB,Palmieri TL,Greenhalgh DD,Circulating leptin and cortisol after burn injury: loss of diurnal patternJ Burn Care RehabilYear: 20042549149910.1097/01.BCR.0000144532.02792.6E15534457
Laviano A,Meguid MM,Rossi-Fanelli F,Improving food intake in anorectic cancer patientsCurr Opin Clin Nutr Metab CareYear: 2003642142612806216
Thaler JP,Choi SJ,Schwartz MW,Wisse BE,Hypothalamic inflammation and energy homeostasis: resolving the paradoxFront NeuroendocrinolYear: 201031798410.1016/j.yfrne.2009.10.00219822168
Pimentel GD,Lira FS,Rosa JC,Oliveira JL,Losinskas-Hachul AC,Souza GI,das Gracas TdCM,Santos RV,de Mello MT,Tufik S,et al. Intake of trans fatty acids during gestation and lactation leads to hypothalamic inflammation via TLR4/NFkappaBp65 signaling in adult offspringJ Nutr BiochemYear: 20122326527110.1016/j.jnutbio.2010.12.00321543208
Pauling L,The Relation between Longevity and Obesity in Human BeingsProc Natl Acad Sci USAYear: 19584461962210.1073/pnas.44.6.61916590251
Hetherington AW RS,Hypothalamic lesions and adiposity in the ratAnat RecYear: 19407814917210.1002/ar.1090780203
Anand BK,Brobeck JR,Hypothalamic control of food intake in rats and catsYale J Biol MedYear: 19512412314014901884
Teitelbaum P,Stellar E,Recovery from the failure to eat produced by hypothalamic lesionsScienceYear: 195412089489510.1126/science.120.3126.89413216188
Miller NE,Experiments on motivation. Studies combining psychological, physiological, and pharmacological techniquesScienceYear: 19571261271127810.1126/science.126.3286.127113495454
Zhang Y,Proenca R,Maffei M,Barone M,Leopold L,Friedman JM,Positional cloning of the mouse obese gene and its human homologueNatureYear: 199437242543210.1038/372425a07984236
Leibowitz SF,Wortley KE,Hypothalamic control of energy balance: different peptides, different functionsPeptidesYear: 20042547350410.1016/j.peptides.2004.02.00615134868
Schwartz MW,Woods SC,Porte D Jr,Seeley RJ,Baskin DG,Central nervous system control of food intakeNatureYear: 200040466167110766253
Valentino MA,Lin JE,Snook AE,Li P,Kim GW,Marszalowicz G,Magee MS,Hyslop T,Schulz S,Waldman SA,A uroguanylin-GUCY2C endocrine axis regulates feeding in miceJ Clin InvestYear: 20111213578358810.1172/JCI5792521865642
Cryan JF,O'Mahony SM,The microbiome-gut-brain axis: from bowel to behaviorNeurogastroenterol MotilYear: 20112318719210.1111/j.1365-2982.2010.01664.x21303428
Mayer EA,Gut feelings: the emerging biology of gut-brain communicationNat Rev NeurosciYear: 20111245346621750565
Bravo JA,Forsythe P,Chew MV,Escaravage E,Savignac HM,Dinan TG,Bienenstock J,Cryan JF,Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerveProc Natl Acad Sci USAYear: 2011108160501605510.1073/pnas.110299910821876150
Grenham S,Clarke G,Cryan JF,Dinan TG,Brain-gut-microbe communication in health and diseaseFront PhysiolYear: 201129422162969
Backhed F,Ley RE,Sonnenburg JL,Peterson DA,Gordon JI,Host-bacterial mutualism in the human intestineScienceYear: 20053071915192010.1126/science.110481615790844
Ley RE,Turnbaugh PJ,Klein S,Gordon JI,Microbial ecology: human gut microbes associated with obesityNatureYear: 20064441022102310.1038/4441022a17183309
Zhang H,DiBaise JK,Zuccolo A,Kudrna D,Braidotti M,Yu Y,Parameswaran P,Crowell MD,Wing R,Rittmann BE,Krajmalnik-Brown R,Human gut microbiota in obesity and after gastric bypassProc Natl Acad Sci USAYear: 20091062365237010.1073/pnas.081260010619164560
Eckburg PB,Bik EM,Bernstein CN,Purdom E,Dethlefsen L,Sargent M,Gill SR,Nelson KE,Relman DA,Diversity of the human intestinal microbial floraScienceYear: 20053081635163810.1126/science.111059115831718
Caricilli AM,Picardi PK,de Abreu LL,Ueno M,Prada PO,Ropelle ER,Hirabara SM,Castoldi A,Vieira P,Camara NO,et al. Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout micePLoS BiolYear: 20119e100121210.1371/journal.pbio.100121222162948
Cummings JH,Pomare EW,Branch WJ,Naylor CP,Macfarlane GT,Short chain fatty acids in human large intestine, portal, hepatic and venous bloodGutYear: 1987281221122710.1136/gut.28.10.12213678950
McNeil NI,The contribution of the large intestine to energy supplies in manAm J Clin NutrYear: 1984393383426320630
Zaibi MS,Stocker CJ,O'Dowd J,Davies A,Bellahcene M,Cawthorne MA,Brown AJ,Smith DM,Arch JR,Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acidsFEBS LettYear: 20105842381238610.1016/j.febslet.2010.04.02720399779
Sekirov I,Russell SL,Antunes LC,Finlay BB,Gut microbiota in health and diseasePhysiol RevYear: 20109085990410.1152/physrev.00045.200920664075
Forsythe P,Sudo N,Dinan T,Taylor VH,Bienenstock J,Mood and gut feelingsBrain Behav ImmunYear: 20102491610.1016/j.bbi.2009.05.05819481599
Ley RE,Backhed F,Turnbaugh P,Lozupone CA,Knight RD,Gordon JI,Obesity alters gut microbial ecologyProc Natl Acad Sci USAYear: 2005102110701107510.1073/pnas.050497810216033867
Turnbaugh PJ,Ley RE,Mahowald MA,Magrini V,Mardis ER,Gordon JI,An obesity-associated gut microbiome with increased capacity for energy harvestNatureYear: 20064441027103110.1038/nature0541417183312
Cani PD,Amar J,Iglesias MA,Poggi M,Knauf C,Bastelica D,Neyrinck AM,Fava F,Tuohy KM,Chabo C,et al. Metabolic endotoxemia initiates obesity and insulin resistanceDiabetesYear: 2007561761177210.2337/db06-149117456850
De Souza CT,Araujo EP,Bordin S,Ashimine R,Zollner RL,Boschero AC,Saad MJ,Velloso LA,Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamusEndocrinologyYear: 20051464192419910.1210/en.2004-152016002529
Zhang X,Zhang G,Zhang H,Karin M,Bai H,Cai D,Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesityCellYear: 2008135617310.1016/j.cell.2008.07.04318854155
Milanski M,Degasperi G,Coope A,Morari J,Denis R,Cintra DE,Tsukumo DM,Anhe G,Amaral ME,Takahashi HK,et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesityJ NeurosciYear: 20092935937019144836
Ropelle ER,Flores MB,Cintra DE,Rocha GZ,Pauli JR,Morari J,de Souza CT,Moraes JC,Prada PO,Guadagnini D,et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibitionPLoS BiolYear: 20108e100046510.1371/journal.pbio.100046520808781
Duarte Pimentel G,Rosa JC,Santos de Lira F,Differences in diet between the 19th and 21st centuries: could they lead to insulin and leptin resistance and inflammation?Endocrinol NutrYear: 20115825225410.1016/j.endonu.2011.02.00721530426
Raybould HE,Gut microbiota, epithelial function and derangements in obesityJ PhysiolYear: 201259044144622183718
Duparc T,Naslain D,Colom A,Muccioli GG,Massaly N,Delzenne NM,Valet P,Cani PD,Knauf C,Jejunum inflammation in obese and diabetic mice impairs enteric glucose detection and modifies nitric oxide release in the hypothalamusAntioxid Redox SignalYear: 20111441542310.1089/ars.2010.333020879900
Ding S,Chi MM,Scull BP,Rigby R,Schwerbrock NM,Magness S,Jobin C,Lund PK,High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mousePLoS OneYear: 20105e1219110.1371/journal.pone.001219120808947
de La Serre CB,Ellis CL,Lee J,Hartman AL,Rutledge JC,Raybould HE,Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammationAm J Physiol Gastrointest Liver PhysiolYear: 2010299G440G44810.1152/ajpgi.00098.201020508158
Monte SV,Caruana JA,Ghanim H,Sia CL,Korzeniewski K,Schentag JJ,Dandona P,Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitusSurgeryYear: 201215158759310.1016/j.surg.2011.09.03822088821
Vinolo MA,Hirabara SM,Curi R,G-protein-coupled receptors as fat sensorsCurr Opin Clin Nutr Metab CareYear: 20121511211610.1097/MCO.0b013e32834f459822234165
Vijay-Kumar M,Aitken JD,Carvalho FA,Cullender TC,Mwangi S,Srinivasan S,Sitaraman SV,Knight R,Ley RE,Gewirtz AT,Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5ScienceYear: 201032822823110.1126/science.117972120203013
Henao-Mejia J,Elinav E,Jin C,Hao L,Mehal WZ,Strowig T,Thaiss CA,Kau AL,Eisenbarth SC,Jurczak MJ,et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesityNatureYear: 201248217918522297845
Wu GD,Chen J,Hoffmann C,Bittinger K,Chen YY,Keilbaugh SA,Bewtra M,Knights D,Walters WA,Knight R,et al. Linking long-term dietary patterns with gut microbial enterotypesScienceYear: 201133410510810.1126/science.120834421885731
Brun P,Castagliuolo I,Di Leo V,Buda A,Pinzani M,Palu G,Martines D,Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitisAm J Physiol Gastrointest Liver PhysiolYear: 2007292G518G52517023554
Suzuki T,Hara H,Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF ratsNutr Metab (Lond)Year: 201071910.1186/1743-7075-7-1920222989
Furuse M,Hirase T,Itoh M,Nagafuchi A,Yonemura S,Tsukita S,Occludin: a novel integral membrane protein localizing at tight junctionsJ Cell BiolYear: 19931231777178810.1083/jcb.123.6.17778276896
Furuse M,Fujita K,Hiiragi T,Fujimoto K,Tsukita S,Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludinJ Cell BiolYear: 19981411539155010.1083/jcb.141.7.15399647647
Martin-Padura I,Lostaglio S,Schneemann M,Williams L,Romano M,Fruscella P,Panzeri C,Stoppacciaro A,Ruco L,Villa A,et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigrationJ Cell BiolYear: 199814211712710.1083/jcb.142.1.1179660867
Gonzalez-Mariscal L,Betanzos A,Nava P,Jaramillo BE,Tight junction proteinsProg Biophys Mol BiolYear: 20038114410.1016/S0079-6107(02)00037-812475568
Cani PD,Bibiloni R,Knauf C,Waget A,Neyrinck AM,Delzenne NM,Burcelin R,Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in miceDiabetesYear: 2008571470148110.2337/db07-140318305141
Osbak PS,Bindslev N,Hansen MB,Relationships between body mass index and short-circuit current in human duodenal and colonic mucosal biopsiesActa Physiol (Oxf)Year: 2011201475310.1111/j.1748-1716.2010.02202.x20950341
Kremen AJ,Linner JH,Nelson CH,An experimental evaluation of the nutritional importance of proximal and distal small intestineAnn SurgYear: 195414043944810.1097/00000658-195409000-0001813198079
Sjostrom L,Peltonen M,Jacobson P,Sjostrom CD,Karason K,Wedel H,Ahlin S,Anveden A,Bengtsson C,Bergmark G,et al. Bariatric surgery and long-term cardiovascular eventsJAMAYear: 2012307566510.1001/jama.2011.191422215166
Evans S,Pamuklar Z,Rosko J,Mahaney P,Jiang N,Park C,Torquati A,Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restrictionSurg EndoscYear: 2012261086109410.1007/s00464-011-2004-722044971
Morinigo R,Moize V,Musri M,Lacy AM,Navarro S,Marin JL,Delgado S,Casamitjana R,Vidal J,Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjectsJ Clin Endocrinol MetabYear: 2006911735174010.1210/jc.2005-090416478824
Falken Y,Hellstrom PM,Holst JJ,Naslund E,Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptidesJ Clin Endocrinol MetabYear: 2011962227223510.1210/jc.2010-287621543426
Beckman LM,Beckman TR,Earthman CP,Changes in gastrointestinal hormones and leptin after Roux-en-Y gastric bypass procedure: a reviewJ Am Diet AssocYear: 201011057158410.1016/j.jada.2009.12.02320338283
Danese S,Fiocchi C,Ulcerative colitisN Engl J MedYear: 20113651713172510.1056/NEJMra110294222047562
Uchino M,Ikeuchi H,Matsuoka H,Matsumoto T,Takesue Y,Tomita N,Clinical features and management of duodenal fistula in patients with Crohn's diseaseHepatogastroenterologyYear: 20125917117422251533
Koloski NA,Jones M,Kalantar J,Weltman M,Zaguirre J,Talley NJ,The brain-gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based studyGutYear: 2012 in press .
Macfarlane S,Macfarlane GT,Regulation of short-chain fatty acid productionProc Nutr SocYear: 200362677210.1079/PNS200220712740060
Walker AW,Sanderson JD,Churcher C,Parkes GC,Hudspith BN,Rayment N,Brostoff J,Parkhill J,Dougan G,Petrovska L,High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel diseaseBMC MicrobiolYear: 201111710.1186/1471-2180-11-721219646
Brint EK,MacSharry J,Fanning A,Shanahan F,Quigley EM,Differential expression of toll-like receptors in patients with irritable bowel syndromeAm J GastroenterolYear: 201110632933610.1038/ajg.2010.43821102570
Cario E,Podolsky DK,Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel diseaseInfect ImmunYear: 2000687010701710.1128/IAI.68.12.7010-7017.200011083826
Dinan TG,Quigley EM,Ahmed SM,Scully P,O'Brien S,O'Mahony L,O'Mahony S,Shanahan F,Keeling PW,Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?GastroenterologyYear: 200613030431110.1053/j.gastro.2005.11.03316472586
Rodriguez-Perlvarez ML,Sanchez VG,Pastor CM,Gonzalez R,Flores EI,Muntane J,Camacho FG,Role of serum cytokine profile in ulcerative colitis assessmentInflamm Bowel DisYear: 2012 in press .
Grijalva CG,Chen L,Delzell E,Baddley JW,Beukelman T,Winthrop KL,Griffin MR,Herrinton LJ,Liu L,Ouellet-Hellstrom R,et al. Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseasesJAMAYear: 20113062331233910.1001/jama.2011.169222056398
Wang K,Yuan CP,Wang W,Yang ZQ,Cui W,Mu LZ,Yue ZP,Yin XL,Hu ZM,Liu JX,Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitisWorld J GastroenterolYear: 2010162252225910.3748/wjg.v16.i18.225220458762
Pavlov VA,Tracey KJ,Neural regulators of innate immune responses and inflammationCell Mol Life SciYear: 2004612322233115378203
Malinen E,Rinttila T,Kajander K,Matto J,Kassinen A,Krogius L,Saarela M,Korpela R,Palva A,Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCRAm J GastroenterolYear: 200510037338210.1111/j.1572-0241.2005.40312.x15667495
Kerckhoffs AP,Samsom M,van der Rest ME,de Vogel J,Knol J,Ben-Amor K,Akkermans LM,Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patientsWorld J GastroenterolYear: 2009152887289210.3748/wjg.15.288719533811
Frank DN,St Amand AL,Feldman RA,Boedeker EC,Harpaz N,Pace NR,Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseasesProc Natl Acad Sci USAYear: 2007104137801378510.1073/pnas.070662510417699621
Rajilic-Stojanovic M,Biagi E,Heilig HG,Kajander K,Kekkonen RA,Tims S,de Vos WM,Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndromeGastroenterologyYear: 20111411792180110.1053/j.gastro.2011.07.04321820992
Cani PD,Neyrinck AM,Fava F,Knauf C,Burcelin RG,Tuohy KM,Gibson GR,Delzenne NM,Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemiaDiabetologiaYear: 2007502374238310.1007/s00125-007-0791-017823788
O'Keefe SJ,Ou J,Delany JP,Curry S,Zoetendal E,Gaskins HR,Gunn S,Effect of fiber supplementation on the microbiota in critically ill patientsWorld J Gastrointest PathophysiolYear: 2011213814510.4291/wjgp.v2.i6.13822180847
Sanz Y,Gut microbiota and probiotics in maternal and infant healthAm J Clin NutrYear: 2011942000S2005S10.3945/ajcn.110.00117221543533
McNulty NP,Yatsunenko T,Hsiao A,Faith JJ,Muegge BD,Goodman AL,Henrissat B,Oozeer R,Cools-Portier S,Gobert G,et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twinsSci Transl MedYear: 20113106ra10610.1126/scitranslmed.3002701
Thomas LV,Ockhuizen T,New insights into the impact of the intestinal microbiota on health and disease: a symposium reportBr J NutrYear: 2012107Suppl 1S1S1322260731
Whorwell PJ,Do probiotics improve symptoms in patients with irritable bowel syndrome?Therap Adv GastroenterolYear: 20092374410.1177/1756283X09335637
Hakansson A,Molin G,Gut microbiota and inflammationNutrientsYear: 2011363768210.3390/nu306063722254115
Zareie M,Johnson-Henry K,Jury J,Yang PC,Ngan BY,McKay DM,Soderholm JD,Perdue MH,Sherman PM,Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stressGutYear: 2006551553156010.1136/gut.2005.08073916638791
Mangell P,Lennernas P,Wang M,Olsson C,Ahrne S,Molin G,Thorlacius H,Jeppsson B,Adhesive capability of Lactobacillus plantarum 299v is important for preventing bacterial translocation in endotoxemic ratsAPMISYear: 200611461161810.1111/j.1600-0463.2006.apm_369.x16948813
Reimer RA,McBurney MI,Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in ratsEndocrinologyYear: 19961373948395610.1210/en.137.9.39488756571
Tarini J,Wolever TM,The fermentable fibre inulin increases postprandial serum short-chain fatty acids and reduces free-fatty acids and ghrelin in healthy subjectsAppl Physiol Nutr MetabYear: 20103591610.1139/H09-11920130660
Everard A,Lazarevic V,Derrien M,Girard M,Muccioli GG,Neyrinck AM,Possemiers S,Van Holle A,Francois P,de Vos WM,et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant miceDiabetesYear: 2011602775278610.2337/db11-022721933985
Roelofsen H,Priebe MG,Vonk RJ,The interaction of short-chain fatty acids with adipose tissue: relevance for prevention of type 2 diabetesBenef MicrobesYear: 2010143343710.3920/BM2010.002821831781
Haska L,Andersson R,Nyman M,A water-soluble fraction from a by-product of wheat increases the formation of propionic acid in rats compared with diets based on other by-product fractions and oligofructoseFood Nutr ResYear: 2011 in press .
Chawla A,Nguyen KD,Goh YP,Macrophage-mediated inflammation in metabolic diseaseNat Rev ImmunolYear: 20111173874910.1038/nri307121984069
Oh DY,Talukdar S,Bae EJ,Imamura T,Morinaga H,Fan W,Li P,Lu WJ,Watkins SM,Olefsky JM,GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effectsCellYear: 201014268769810.1016/j.cell.2010.07.04120813258
Cunningham-Rundles S,Ahrne S,Johann-Liang R,Abuav R,Dunn-Navarra AM,Grassey C,Bengmark S,Cervia JS,Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infectionNutrientsYear: 201131042107010.3390/nu312104222292110
Compare D,Nardone G,Contribution of gut microbiota to colonic and extracolonic cancer developmentDig DisYear: 20112955456110.1159/00033296722179211
Pimentel GD,Portero-McLellan KC,Oliveira EP,Spada AP,Oshiiwa M,Zemdegs JC,Barbalho SM,Long-term nutrition education reduces several risk factors for type 2 diabetes mellitus in Brazilians with impaired glucose toleranceNutr ResYear: 20103018619010.1016/j.nutres.2010.03.00320417879
Pimentel GD,Arimura ST,de Moura BM,Silva ME,de Sousa MV,Short-term nutritional counseling reduces body mass index, waist circumference, triceps skinfold and triglycerides in women with metabolic syndromeDiabetol Metab SyndrYear: 201021310.1186/1758-5996-2-1320181143
Kau AL,Ahern PP,Griffin NW,Goodman AL,Gordon JI,Human nutrition, the gut microbiome and the immune systemNatureYear: 201147432733610.1038/nature1021321677749


[Figure ID: F1]
Figure 1 

Role of gut hormones in fasting (right) and postprandial (left) state. During fasting, occurs greater release of ghrelin from the stomach that acts in arcuate nucleus via vagus nerve stimulating hunger. During the fed state (postprandial), occurs release of anorexigenic hormones (GLP-1, OXM, PYY, CCK and GIP) that reach the arcuate nucleus via the brainstem and vagus nerve, activating the satiety. GLP-1: glucagon-like peptide 1, OXM: oxyntomodulin, PYY: peptide YY, CCK: cholecystokinin, GIP: glucose-dependent insulinotropic polypeptide.

[Figure ID: F2]
Figure 2 

Role of gut-central nervous system axis on inflammatory diseases.

[Figure ID: F3]
Figure 3 

Secretion sities of anorexigenic hormones, such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) are increased after bariatric surgery.

[Figure ID: F4]
Figure 4 

Summary of main physiological and metabolic alterations that modify the gut sick and health before and after the nutritional therapies.

[Figure ID: F5]
Figure 5 

Role of intestinal microbiota on development or prevention of inflammatory diseases via dietary fibers, probiotic or prebiotic in the peripheral tissues and central nervous system. ZO-1: Zonula Occludens, JAM-1: juntional adhesion molecule 1.

[TableWrap ID: T1] Table 1 

Summary of the main gut hormones that influence the energy homeostasis

Gut hormones (receptor) Secretion site Action
PYY (G protein-coupled receptors) L cells of gut ↓ food intake and delays gastric emptying
GLP-1 (GLP-1R) L cells of gut ↓ food intake, releases insulin, hand out as incretin, ↓ glucose levels and delays gastric emptying
OXM (GLP-1R) L cells of gut ↓ food intake
CCK (CCK1 and CCK2) I cell of small intestine ↓ food intake
Uroguanylin and Guanylin (GUCY2CR) Intestinal epithelial cells ↓ food intake
GIP K cells of gut ↓ food intake and glucose levels
PP (Y4 and Y5) PP cells of pancreas ↓ food intake
Amylin (AMY 1-3) β cells of pancreas ↓ glucose levels
Insulin (IR) β cells of pancreas ↓ food intake and glucose levels
Glucagon (GCGR) α cells of pancreas ↑ glucose levels and insulin secretion
Ghrelin (GHSR1) Stomach ↑ food intake

PYY: peptide tyrosine tyrosine; GLP-1: glucagon-like peptide 1; PP: pancreatic polypeptide; OXM: oxyntomodulin; CCK: cholecystokinin; GHSR1: growth hormone secretagogue; GUCY2C receptors: guanylyl cyclase 2 C receptors; IR: insulin receptor; GIP: glucose-dependent insulinotropic peptide.

Article Categories:
  • Review

Keywords: Gut, Central nervous system, Nutrition, Diet, Appetite, Inflammatory disease.

Previous Document:  Lysolipid containing liposomes for transendothelial drug delivery.
Next Document:  Out-of-hospital Cardiac Arrest Outcomes Stratified By Rhythm Analysis.