OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. ...

Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the ...

Latin America is undergoing a rapid demographic and nutritional transition. A recent WHO/PAHO survey on obesity in the region revealed an increasing trend in obesity as countries emerge from poverty, especially in urban areas. In contrast, in middle income countries, obesity tends to decline as income increases; this is especially ...

OBJECTIVE: Sympathetic nervous system abnormality in humans is still a matter of debate. The present study was designed to examine diet-induced autonomic nervous system activity and metabolic change in obese and non-obese young women. RESEARCH METHODS AND PROCEDURES: Sixteen age- and height-matched obese and non-obese young women participated in this ...

The etiology of obesity involves imbalanced energy intake and utilization. ASP is an adipose tissue hormone that facilitates adipocyte uptake of serum fatty acids and their storage. Mice lacking ASP have less adipose tissue mass, despite increased food intake, than wild-type littermates. We hypothesize that the unstored fuels are oxidized ...

1. Leptin is secreted by fat and acts on the brain. 2. Central infusion of leptin reduces food intake but does not alter endocrine secretions in normally fed sheep. 3. Leptin treatment can correct for altered hormonal secretion in fasted animals. 4. Alterations in bodyweight (leptin status) affect the expression ...

We describe the radiographic findings observed in a morbidly obese and diabetic patient with an intragastric air-filled balloon introduced as a therapeutic measure to reduce food intake. The balloon was associated with chronic gastric dilatation and had to be removed 3 months after insertion. However, together with diet and behavioural ...

Leptin, a 16 kDa protein encoded by the ob gene, is known mainly for its role in the regulation of food intake, body composition and energy expenditure through a central feedback mechanism. Initially leptin was considered as an ob gene product of adipocytes but recently the presence of leptin and ...

The brain plays a key role in the regulation of energy homeostasis, balancing food intake and energy expenditure to maintain adipose tissue mass. A widely accepted model proposes that energy homeostasis is modulated by hormones that circulate in the blood in proportion to adipose tissue mass. A major candidate 'adiposity ...

A major advance in the understanding of the control of appetite, food intake, and energy expenditure came with the discovery of leptin. Leptin concentrations correlate with adipose tissue mass, and leptin acts via the central nervous system (CNS) to reduce food intake and increase energy expenditure. A variety of different ...

The annual meeting of the North American Association for the Study of Obesity was held in Long Beach, CA, USA with approximately 1500 attendees, including basic and clinical obesity/food intake researchers and local and regional physicians. The meeting highlighted a clear trend toward pharmacological approaches directed at the brain control ...

Successful reproduction requires the accumulation of energy reserves. Although acute and chronic food deprivation disrupts reproduction, surprisingly, an over-abundance of energy reserves can also result in infertility. The infertility of obese, ob/ob mice can be reversed by the reintroduction of leptin, the protein product of the ob gene. In rats, ...

It is well known that leptin plays a predominant role in body weight regulation. Leptin receptors are especially abundant in the hypothalamus, where the majority of leptin's biologic activity occurs. In instances where leptin has no or limited activity, it is easy to implicate leptin resistance and speculate as to ...

In order to study the role of vagus nerve activity at the onset of obesity induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or sham operated. Body weight and food intake were recorded until animals were 90 days old and then sacrificed. Naso-anal length was recorded for all animals. ...

Recently, hypocretins have been implicated in the pathophysiology of narcolepsy, a sleep disorder characterized particularly by the occurrence of excessive daytime sleepiness and cataplexy. Hypocretins, which stimulate food intake, have been reported to be absent in the cerebrospinal fluid (CSF) of the majority of patients suffering from narcolepsy. Because these ...

We have previously shown that morning administration of dexamethasone in combination with food induces a doubling of serum leptin levels starting at 7 hours after dexamethasone administration, with a maximum effect at 10 hours, the latest time point that we have studied. However, dexamethasone given in the absence of food ...

Recent technologic innovations have enabled probing the workings of individual cells and even molecules. As a result, our knowledge of the biological controls over eating and the regulation of body adiposity is increasing at a rapid pace. We review the evidence that food intake is controlled by separate but interacting ...

The epidemic diffusion of obesity in industrialised countries has promoted research on the aetiopathogenesis of this disorder. The purpose of this review is to focus mainly on the contribution that European research has made to this field. Available evidence suggests that obesity results from multiple interactions between genes and environment. ...

Several regulatory substances participate in the regulation of both food intake/energy metabolism and reproduction in mammals. Most of these neuropeptides originate and act in the central nervous system, mainly at specific hypothalamic areas. Leptin represents a signal integrating all these functions, but originating from the periphery (adipose tissue) and carrying ...

We investigated the long-term effects of physiological levels of leptin produced by gene therapy on body weight (BW) and expression of genes that encode orexigenic and anorexigenic peptides in the hypothalamus. Recombinant adeno-associated viral vector (rAAV), a non-pathogenic and non-immunogenic vector, encoding leptin (betaOb) was generated and administered iv to ...

Leptin, the product of the ob gene, is a hormone secreted by adipocytes that regulates food intake and energy expenditure. The hypothalamus-pituitary-thyroid axis is markedly influenced by the metabolic status, being suppressed during food deprivation. The aim of the present study was to assess whether leptin can act as a ...

It is widely believed that the primary physiologic role of leptin is to prevent obesity by regulating food intake and thermogenesis through actions on hypothalamic centers. Here we sugest that the first premise, the anti-obesity role, is untenable, and present evidence for an alternative physiologic role, namely antisteatotic activity in ...

The aetiology and treatment of obesity have been fraught with disappointment for researchers, because the mechanisms that control fuel homeostasis and adiposity are incompletely understood. It is assumed that regulatory processes match the dietary fuel supply with energy requirements in order to maintain a stable body mass and adiposity. In ...

OBJECTIVE: To determine if the source from which food is obtained has contributed to the increased obesity of the US population, while controlling for demographic, lifestyle and regional factors. METHODS: Multiple regression was used to estimate the effect of food source on body mass index (BMI) while accounting for other ...

Obesity could well become the most common health problem of the 21st century. There are more opportunities to consume large quantities of food: big portions of tasty, varied food, at reasonable prices, are available everywhere. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, ...

Insulin and leptin receptors are present in hypothalamic regions that control energy homeostasis, and these hormones reduce food intake and body weight in lean, but not obese, Zucker rats. Here we demonstrate that insulin, like leptin, hyperpolarizes lean rat hypothalamic glucose-responsive (GR) neurons by opening KATP channels. These findings suggest ...

Obesity represents a growing threat for the health of population worldwide. The decline of physical activity and the passive overconsumption of energy-dense, high-fat diets are important factors that explain the increased prevalence of obesity. Despite many efforts, the prevention and the treatment of obesity are often a failure. Since obesity ...

Study of neurotransmitter role in food intake regulation in a leptin signaling deficient model, such as the Zucker rat, would benefit in the understanding of mechanisms of human obesity, in which leptin resistance is a common syndrome. We studied dopamine (DA) and serotonin (5-HT) concentrations in vivo in the ventromedial ...

The chicken leptin sequence, in contrast to mammalian leptins, contains an unpaired Cys at position 3 of the original cDNA (AF012727). The presence of an extra Cys may confer a different structure and affect the leptin's biological activity. To address this, we studied the effects of wild-type and mutated (C4S) ...

Regulatory thermogenesis occurs upon exposure to the cold or during food intake. Among a variety of mechanisms leading to heat production, uncoupling of respiration in brown adipocyte mitochondria appears to be a major contributor to resistance to the cold in rodents. This uncoupling mechanism is due to the activity of ...

OBJECTIVE: The extent to which leptin protects against obesity is unknown. By intercrossing New Zealand obese mice with lean C57BL/6J mice, we have separated the genes controlling leptin and other weight-related phenotypes. This has allowed us to determine whether hyperleptinaemia is associated with reduced food intake and increased physical activity ...

Recent experimental evidence supports the role of glucocorticoids in the neuroendocrine control of food intake and energy expenditure. In particular, glucocorticoids promote food consumption directly through stimulation of NPY and inhibition of CRH and melanocortin release. CRH and NPY are also functionally linked by a mutual regulation. CRH is anorexigenic ...

Food deprivation and adrenalectomy are associated with low concentrations of leptin in blood and the absence of obesity. Because leptin is known to cross the blood-brain barrier (BBB) by a saturable transport system, we examined whether fasting and adrenalectomy (ADX) also act at the BBB. Multiple-time regression analysis showed that ...

The effect of intracerebroventricular (i.c.v.) injection of leptin was investigated using broiler and Single Comb White Leghorn (SCWL)-type chickens. These represent relatively fast- and slow-growing birds, respectively. The i.c.v. injection of leptin decreased food intake in both broilers and Leghorns in a dose-dependent manner. The most efficacious dose appeared to ...

In the field of obesity research, two separate lines of study have emerged which explore the mechanism by which food intake is regulated: short-term control of food intake, and the central regulation of energy balance. The former studies the satiety response during consumption of meals, whereby satiety signalling originating in ...

The actions of intracerebroventricularly (i.c.v.) infused leptin on food intake, body weight and hypothalamic contents of histamine and tele-methylhistamine, the main histamine metabolite in the mammalian brain, were studied in male Wistar rats. The effect of the histamine H(1) receptor blockade on leptin-induced anorexia was also examined. It was found ...

This study was intended for the investigation of the effects of chronic injections of leptin for 7 days on food intake and hypothalamic neurotensin (NT). Leptin treatment significantly reduced food intake [144.3+/-2.5 g (L) vs. 156.7+/-2.5 g (C); P=0. 002] and body weight gain [23.7 g+/-1.0 g (L) vs. 31.5+/-1.3 ...

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of ...

Orexins, which are identical to hypocretins, are novel hypothalamic orexigenic peptides. We examined the effects of food restriction on the expression of the prepro-orexin gene in control (C57Bl/6J) and genetically obese mice (ob/ob and db/db), using in situ hybridization histochemistry. Dry food was given 3 g/day to each obese mouse ...

Selection for high or low daily food intake (DFI) in Large White pigs resulted in higher serum leptin concentration, fat deposition and food intake in the high DFI line. The response in serum leptin concentration indicated that the higher fat deposition of the high DFI line was not due to ...

Leptin, the adipocyte-derived plasma hormone, and CNS GLP-1 neurons reduce food intake and body weight. GLP-1 is produced in the CNS by post-translational processing of pre-proglucagon. ICV leptin administration prevented the reduction in hypothalamic GLP-1 peptide content seen in pair-fed food-restricted rats (P < 0.05). There was a significant overall ...

This paper reviews the general mechanisms by which leptin acts as a regulator of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid metabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. ...

Energy expenditure in ob/ob mice kept at thermoneutrality was quantified from food intake and body composition of mice treated with leptin over 15 and 75 days, respectively. Energy expenditure in response to 15 days of treatment with leptin was twice as high as under pair-feeding conditions, indicating extensive breakdown of ...

The prevalence of obesity is reaching epidemic proportions in many industrialized countries. There is growing evidence that, even if the trigger of this epidemic is found in changes in the environment, genes are interacting with the environment to cause weight gain. Studies of twins reared apart indicate that approximately two-thirds ...

The microstructure of eating behavior reflects physical properties of food. Responses of lean and obese subjects to these physical properties are similar. For example, eating smaller bite-sized food units reduces initial ingestion rate and mean and local ingestion rate for the entire meal, but does not affect total intake in ...

Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss. To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration. At five stimulation sites near the fornix, the effectiveness of the ...

Mean daily intake of all foods except cereals i.e. pulses, green leafy vegetables, roots and tubers, fruits, milk and milk products, sugar and fats of Indian obese male respondents was higher than the values recommended by Indian Council of Medical Research (ICMR, 1987). The consumption of fat and sugar was ...

Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this ...

Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant ...

BACKGROUND/AIMS: Leptin, the ob/ob gene product, is a recently discovered peptide hormone, secreted by adipocytes, which can act as a satiety factor to regulate food intake. Its levels thus will be related to the presence of food in the lumen of the gut, and food intake is one of the ...