Alaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward ...

Cigarette smoke is composed of over 4000 chemicals many of which are strong oxidizing agents and chemical carcinogens. Chronic cigarette smoke exposure (CSE) induces mild alterations in liver histology indicative of toxicity though the molecular pathways underlying these alterations remain to be explored. Utilizing a mouse model of 'active' developmental ...

The Brenner hypothesis states that a congenital reduction in nephron number predisposes to adult-onset hypertension and renal failure. The reduction in nephron number induced by proportionally smaller kidney mass may predispose offspring to glomerular hyperfiltration with maturity onset obesity. Developmental cigarette smoke exposure (CSE) results in intrauterine growth retardation with ...

Naringin is a flavanone with various bioactivities including expectorant effect, antitussive effect and inhibitory effects on asthma and acute lung injury. In present study we examined the effects of naringin on enhanced cough, airway hyperresponsiveness (AHR) and airway inflammation in chronic cigarette smoke (CS) exposure-induced chronic bronchitis in guinea pigs. ...

Nicotine metabolism and genetic variation have an impact on nicotine addiction and smoking abstinence; however, further research is required. The nicotine metabolite ratio (NMR) is a robust biomarker of nicotine metabolism used to categorize slow and normal nicotine metabolizers (lower 25th quartile cut off). In two randomized clinical trials of ...

Cigarette smoke is a risk factor for human health, and many studies were conducted to investigate its adverse effects on humans and other mammals. However, since large amounts of cigarette products are produced and consumed, it is possible that tobacco chemicals can end up in aquatic environments through several routes, ...

Smoking cues trigger craving for cigarettes and relapse. Nicotine metabolism, mediated by the enzyme CYP2A6, also influences smoking behavior. In this study, we investigated how nicotine metabolism and genetic variation in CYP2A6 influence the neural response to smoking cues in humans using functional magnetic resonance imaging (fMRI). We hypothesized that ...

Calcific uremic arteriolopathy, formerly known as calciphylaxis is a devastating condition that primarily affects patients with end-stage renal disease. The lesions can progress to massive ulcerations of the subcutaneous tissue that are associated with a high degree of morbidity and mortality, usually related to sepsis. Although the pathophysiology of this ...

The metabolism of hyperforin, one of the pharmacologically most active components of St. John's wort (Hypericum perforatum), was characterized in vitro using human liver microsomes and recombinant heterologously expressed P450 enzymes. A total of 57 hyperforin metabolites were detected. Of those, six were identified as monohydroxylations (M1-M6), while the others ...

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial ...

Accumulating evidence highlights intriguing interplays between circadian and metabolic pathways. We show that PER2 directly and specifically represses PPARγ, a nuclear receptor critical in adipogenesis, insulin sensitivity, and inflammatory response. PER2-deficient mice display altered lipid metabolism with drastic reduction of total triacylglycerol and nonesterified fatty acids. PER2 exerts its inhibitory ...

Recent studies have revealed a close relationship between inflammatory and metabolic pathways, and inflammation is now recognized to have a major role in obesity and metabolic diseases such as insulin resistance and atherosclerosis. The human body is home to a large number of distinct microbial communities, with the densest population ...

Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress ...

Seabirds differ dramatically in life history traits and breeding strategies. For example, gulls have short incubation shifts (several hours) and high metabolic rates, auks have medium-length incubation shifts (12-24h) and high metabolic rates, and petrels have long incubation shifts (days) and low metabolic rates. How these different strategies affect the ...

We consider recent developments in disorders affecting three areas of metabolism: glycogen, fatty acids, and the mitochondrial respiratory chain. Among the glycogenoses, new attention has been directed to defects of glycogen synthesis resulting in absence rather than excess of muscle glycogen ("aglycogenosis"). These include defects of glycogen synthetase and defects ...

Zebrafish fat-free mutants (ffr) exhibit defective intestinal lipid metabolism and fat-free protein (Ffr) is involved in Golgi-related vesicular trafficking. In this study, we show that ffr mutants also display defective glucose metabolism. Using microarray and real-time PCR, we found that a ffr mutant with a nonsense mutation exhibits increased transcript ...

Objective:  Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may also be involved in migraine-related metabolic alterations like an atherogenic lipid profile and hyperinsulinemia. The aim of this study was to investigate the impact of MMPs and TIMPs on ...

Nuclear receptor crosstalk represents an important mechanism to expand the functions of individual receptors. The liver X receptors (LXR, NR1H2/3), both the α and β isoforms, are nuclear receptors that can be activated by the endogenous oxysterols and other synthetic agonists. LXRs function as cholesterol sensors, which protect mammals from ...

A novel molecular mechanism for the regulation of lipid metabolism by palmitate, H2O2 and the anti-diabetic sulfonylurea drug, glimepiride, in rat adipocytes was recently elucidated. It encompasses the translocation of the glycosylphosphatidylinositol-anchored (GPI-) and (c)AMP degrading enzymes Gce1 and CD73 from detergent-insoluble glycolipid-enriched microdomains of the plasma membrane (DIGs) to ...

Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse ...

OBJECTIVE: Metabolic syndrome and elevated lipids, related to cardiovascular risk factors, are more prevalent in schizophrenia and there has been much debate about the extent to which specific antipsychotics contribute more to the increased risk of developing hyperlipidemia and metabolic syndrome. Most studies have concentrated on fasting levels in patients ...

Little attention has been given to the impact of lipid metabolism on hair follicle biology and pathology. Three recent papers (one in the current issue) describe a major effect of altered lipid metabolism on hair growth. A direct link was made to at least one form of cicatricial alopecia, but ...

Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly ...

The nematode Caenorhabditis elegans (C. elegans) has during the last decade emerged as an invaluable eukaryotic model organism to understand the metabolic and neuro-endocrine regulation of lipid accumulation. The fundamental pathways of food intake, digestion, metabolism, and signalling are evolutionary conserved between mammals and worms making C. elegans a genetically ...

The strong relationship between over-nutrition, central obesity, insulin resistance/metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) suggest pathogenic interactions, but key questions remain. NAFLD starts with over-nutrition, imbalance between energy input and output for which the roles of genetic predisposition and environmental factors (diet, physical activity) are being redefined. Regulation ...

Fibroblast growth factor-21 (FGF-21) has been proposed as a novel metabolic regulator, and animal experiments suggested that FGF-21 may affect energy balance. In humans, FGF-21 was correlated with obesity. Until now, no data exist regarding the relationship of FGF-21 and weight reduction in humans. We therefore investigated whether FGF-21 is ...

Obesity is a growing problem that threatens the health and welfare of a large proportion of the human population. The n-3 polyunsaturated fatty acids (PUFA) are dietary factors that have potential to facilitate reduction in body fat deposition and improve obesity-induced metabolic syndromes. The n-3 PUFA up-regulate several inflammation molecules ...

Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated. We hypothesized that in FPLD, insulin resistance and impaired aerobic ...

The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base ...

Autophagy is a lysosomal degradative pathway critical for the removal and breakdown of cellular components such as organelles and proteins. Despite striking similarities in the regulation and function of autophagy and lipid metabolism, the two processes have only recently been shown to be interrelated. This review details new findings of ...

OBJECTIVE: Postprandial (pp) lipid metabolism is associated with insulin resistance and type 2 diabetes. In young men, pp triglycerides (TGs) are more strongly associated with traits of metabolic syndrome (MS) than fasting TGs. We established a cohort of middle-aged men selected for traits of MS and pp lipid metabolism to ...

Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4-deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of ...

Peroxisomes play an essential role in cellular lipid metabolism as exemplified by the existence of a number of genetic diseases in humans caused by the impaired function of one of the peroxisomal enzymes involved in lipid metabolism. Key pathways in which peroxisomes are involved include: (1.) fatty acid beta-oxidation; (2.) ...

Lipotoxicity is the pathological consequence of lipid overflow in non-adipose tissue, mediated through reactive lipid moieties which may even lead to lipid-induced cell death (lipoapoptosis). This derailment of cellular and organismal fat homeostasis is the consequence of obesity due to continued over-feeding, and contributes substantially to the pathogenesis of insulin ...

Objective: We present the available data on the effects of combined therapy of fenofibrate with drugs affecting lipid metabolism other than statins. Methods: We consider studies evaluating the effects of combined therapy of fenofibrate with bile acid sequestrants (BAS), ezetimibe, niacin, n-3 fatty acids, plant sterols, orlistat, rimonabant, metformin and ...

The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose, and xenobiotic metabolism. Impairment of this rhythm has been shown to lead to diverse pathologies, including metabolic syndrome. Currently, it is supposed that the circadian clock regulates metabolism mostly by regulating expression of liver ...

Macroautophagy (henceforth referred to as autophagy) is an in-bulk lysosomal degradative pathway that plays a crucial role in the maintenance of cellular homeostasis through the removal of damaged proteins and aged organelles. Following nutrient deprivation, a primary cellular response is the induction of autophagy that breaks down redundant cellular components ...

The Gastrointestinal Motility Monitor (GIMM; Catamount Research and Development; St. Albans, VT) is an in vitro system that monitors propulsive motility in isolated segments of guinea pig distal colon. The complete system consists of a computer, video camera, illuminated organ bath, peristaltic and heated water bath circulating pumps, and custom ...

The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. ...

Lipid metabolism is highly relevant as it plays a central role in a number of human diseases. Due to the highly interactive structure of lipid metabolism and its regulation, it is necessary to apply a holistic approach, and systems biology is therefore well suited for integrated analysis of lipid metabolism. ...

Oil-in-water emulsions are used as vaccine adjuvants, but the mechanism of action remains unknown. In this paper we used phagocytes (monocytes, macrophages, dendritic cells) and non-phagocytic cells (fibroblasts, skeletal muscle cells) to study internalization of emulsions in vitro, and to characterize the influence of emulsion uptake on cellular metabolism of ...

Members of the sirtuin family of NAD(+)-dependent protein deacetylases are important regulators of longevity in yeast, worms, and flies. Mammals have seven sirtuins (SIRT1-7), each characterized by differences in subcellular localization, substrate preference, and biological function. While it is unclear whether sirtuins regulate aging in mammals, it is clear that ...

Lipid signaling pathways define central mechanisms for cellular regulation. Productive lipid signaling requires an orchestrated coupling between lipid metabolism, lipid organization and the action of protein machines that execute appropriate downstream reactions. Using membrane trafficking control as primary context, we explore the idea that the Sec14-protein superfamily defines a set ...

It is well established that the development of NAFLD and NASH are closely linked to an excess flow of free fatty acids (FFA) arising from dysfunctional/insulin resistant adipose tissue causing ectopic fat deposition in many organs. In the liver, when chronic lipid supply surpasses the metabolic ability to adapt it ...

This study examined the postprandial metabolism and swimming speed of southern bluefin tuna Thunnus maccoyii when fed sardines Sardinops sagax of either high-lipid and high-energy content or low-lipid and low-energy content. Five groups of two or three T. maccoyii (mean+/-s.e. mass=19.8+/-0.5 kg, n=14) were fed either low [2.2% lipid, 5.5 ...

Experimental studies in GH-deficient patients and in healthy subjects receiving somatostatin-infusion suggest that GH is an important regulator of substrate metabolism during fasting. These models may not adequately reflect the selective effects of GH, and GH receptor (GHR) blockade offers a new model to define the metabolic role of GH. ...

Higher fat and lower carbohydrate and amino acid oxidation are observed in women compared with men during endurance exercise. We hypothesized that the observed sex difference is due to estrogen and that menstrual cycle phase or supplementation of men with 17beta-estradiol (E(2)) would coordinately influence the mRNA content of genes ...

As a multifunctional cytokine, tumor necrosis factor alpha (TNF-alpha) exerts a series of biological actions in different cells, tissues, organs, and species and has been demonstrated to regulate and interfere with energy metabolism, especially lipid homeostasis. A large body of researches suggested that the effects of TNF-alpha on lipid metabolism ...

Maintenance of homeostasis during environmental flux requires constant metabolic adjustment, achieved partly through the fine regulation of gene expression. MicroRNAs are key players in this regulatory milieu; they have been implicated in regulating gene expression within several metabolically active tissues including the endocrine pancreas, liver and adipose tissue. Recent studies, ...

The method concerning in vivo proton HR-MAS NMR metabolic profiling of the freshwater cladoceran Daphnia magna is presented. Viability tests of D. magna under different spinning rates were performed. All surviving daphnids after analysis have developed eggs and embryos like control animals. Better survival rate at the slowest rotation speed ...