Regulation Of Body Fat Research Articles

Serum leptin in obesity is related to gender and body fat topography but does not predict successful weight loss.

Leptin is the product of the ob gene shown to regulate body fat and appetite in mice. It is produced by human adipose tissue also, but its physiological functions in man are poorly known. We studied serum leptin concentrations in ten obese men and 35 obese women (age and body mass index 42 +/- 7 years and 35.1 +/- 3.6 kg/m2 respectively) before (baseline) and at 17 and 57 weeks during weight loss of 10.9% of the initial weight. Serum leptin concentrations at baseline were 55% higher in women than in men (after adjustment for age and body fat mass, P = 0.002) and remained so during the follow-up. At baseline, serum leptin correlated with fat mass (r = 0.60, P < 0.001) estimated by bioelectrical impedance, and the changes in leptin concentrations from baseline to week 17 correlated with the changes in fat mass (r = 0.73, P < 0.001), but baseline leptin levels were not predictive of the successful weight loss. Leptin concentrations correlated with hip circumference (r = 0.49, P < 0.001 at baseline adjusted for age and sex), but the correlation with waist circumference became evident only during the weight loss (at week 57, r = 0.63, P < 0.001). Serum leptin concentrations are higher in obese women than in obese men before and during weight loss, but the topography of fat tissue influences serum leptin concentrations. Serum leptin concentrations do not predict the response to weight reduction.

The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure.

Leptin is an adipocyte-derived hormone that interacts with a putative receptor(s) in the hypothalamus to regulate body weight. The relationship of leptin to metabolic abnormalities associated with obesity together with hormonal and substrate regulation of leptin have not been extensively studied. Therefore, 116 subjects (62 men and 54 women) with a wide range of body weight [body mass index (BMI), 17-54 kg/m2] were characterized on a metabolic ward with regard to body composition, glucose intolerance, insulin sensitivity, energy expenditure, substrate utilization, and blood pressure. Eighty-five of the subjects had normal glucose tolerance (50 men and 35 women), and 31 had noninsulin-dependent diabetes mellitus (12 men and 19 women). In both men and women, fasting leptin levels were highly correlated with BMI (r = 0.87 and r = 0.88, respectively) and percent body fat (r = 0.82 and r = 0.88, respectively; all P < 0.0001). However, men exhibited lower leptin levels at any given measure of obesity. Compared with those in men, leptin levels rose 3.4-fold more rapidly as a function of BMI in women [leptin = 1.815 (BMI)-31.103 in women; leptin = 0.534 (BMI)-8.437 in men] and 3.2 times more rapidly as a function of body fat [leptin = 1.293 (% body fat)-24.817 in women; leptin = 0.402 (% body fat)-3.087 in men]. Hyperleptinemia was associated with insulin resistance (r = -0.57; P < 0.0001) and high waist to hip ratio (r = 0.75; P < 0.0001) only in men. On the other hand, during the hyperinsulinemic euglycemic clamp studies, hyperinsulinemia acutely increased leptin concentrations (20%) only in women. There was no correlation noted between fasting leptin levels and either resting energy expenditure or insulin-induced thermogenesis in men or women (P = NS). In stepwise and multiple regression models with leptin as the dependent variable, noninsulin-dependent diabetes mellitus did not enter the equations at a statistically significant level. The data indicate that there are important gender-based differences in the regulation and action of leptin in humans. Serum leptin levels increase with progressive obesity in both men and women. However, for any given measure of obesity, leptin levels are higher in women than in men, consistent with a state of relative leptin resistance. These findings have important implications regarding differences in body composition in men and women. The observation that serum leptin is not related to energy expenditure rates suggests that leptin regulates body fat predominantly by altering eating behavior rather than calorigenesis.

A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2

Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10(-7)). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) and pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.

Effects of glucocorticoids and of growth hormone on serum leptin concentrations in man.

Recent data suggest an involvement of the ob gene and its product leptin in the regulation of body fat. To assess the effects of glucocorticoids and growth hormone (GH) on serum leptin and body fat, 30 normal subjects received methylprednisolone (0.5 mg.kg-1.day-1) per os for 7 days and 15 subjects received in addition sc injections of GH (0.15 IU.kg-1.day-1) twice daily (combination group). Serum leptin levels increased both in the glucocorticoid group (p < 0.02) and in the combination group (p < 0.002). When body fat was estimated by bioelectrical impedance analysis it decreased during combined treatment and remained unchanged in the glucocorticoid group. Plasma insulin concentrations increased in both groups. Resting energy expenditure (indirect calorimetry) increased in the combination group and remained unchanged in the glucocorticoid group. The finding of increased serum leptin concentrations during treatment with glucocorticoid and GH suggests that serum leptin is regulated by glucocorticoids, possibly though changes in insulin secretion, independently of changes of body fat mass.

Weight-reducing effects of the plasma protein encoded by the obese gene.

The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.

Body fat regulation after partial lipectomy in Siberian hamsters is photoperiod dependent and fat pad specific

Siberian hamsters exhibit seasonal fluctuations in body weight (fat). Initial exposure to a short photoperiod results in body fat loss that reverses after approximately 22 wk of short-day exposure. The purpose of this study was to determine whether Siberian hamsters are able to recover body fat after surgical reduction of total lipid stores and if so, whether this ability is photoperiod dependent and fat pad specific. Either the largest pair of internal fat pads, the epididymal white adipose tissue (EWAT) or one pair of two large external depots, the inguinal (IWAT) fat pads, were removed from male hamsters housed for 22 wk in a long (LD) or short (SD) photoperiod. Retroperitoneal fat pad (RWAT) mass was increased in LD EWAT- and IWAT-lipectomized hamsters. IWAT mass also was increased in the LD EWAT-lipectomized hamsters. Neither SD-lipectomized group compensated for body fat loss in any of the measured fat pads. Increased food intake was not necessary for total body fat recovery, but undereating partially may be responsible for the lack of recovery in SDs. The results of these experiments demonstrate a photoperiod-dependent ability of male Siberian hamsters to regulate total body fat after partial lipectomy. In addition, recovery involves a fat pad-specific compensatory response to partial lipectomy, rather than a general increase in lipid deposition in all fat depots.

Role of set‐point theory in regulation of body weight

In adult individuals body weight is maintained at a relatively stable level for long periods. The set-point theory suggests that body weight is regulated at a predetermined, or preferred, level by a feedback control mechanism. Information from the periphery is carried by an affector to a central controller located in the hypothalamus. The controller integrates and transduces the information into an effector signal that modulates food intake or energy expenditure to correct any deviations in body weight from set-point. Evidence for involvement of various factors and physiological systems in the control of food intake and regulation of body weight and fat are reviewed within the context of a control model. Current working hypotheses include roles for nutrients, dietary composition and organoleptic properties, hormones, neural pathways, various brain nuclei, and many neurotransmitters in the regulation of food intake. It is concluded that regulation of body weight in relation to one specific parameter related to energy balance is unrealistic. It seems appropriate to assume that the level at which body weight and body fat content are maintained represents the equilibria achieved by regulation of many parameters.

1989 McCollum Award lecture. Genetic and hypothalamic mechanisms for obesity--finding the needle in the haystack

The elements of a feedback system for regulating body fat stores consists of an afferent limb providing feedback signals to the central controller in the brain, which integrates information from the sensory and autonomic nervous systems with signals from the internal milieu and modulates ingestive behavior and thermogenic components of the adrenergic nervous system. The search for defective mechanisms that produce obesity has utilized animals with genetic, hypothalamic, and dietary types of obesity. In all three cases, obesity is associated with an absolute or relative decrease in the activity of the sympathetic nervous system. Experimental situations associated with reduced activity of the sympathetic nervous system are generally accompanied by increased food intake and vice versa. Hypothalamic obesity results from damage to the ventromedial hypothalamus, which disrupts modulation of the autonomic nervous system by nutrient and hormonal signals. Recessively inherited obesity may result from failure to modulate the steroid-receptor complex interaction with the promoter region of the genome. Impaired acetylation of melanocyte-stimulating hormone (MSH) may be involved in the development of obesity in the obese yellow mouse. In all cases adrenalectomy arrests the progression or reverses the obesity. These findings further strengthen the autonomic and endocrine hypothesis for obesity.

Fattening responses to daily intervals of heat exposure in the syrian hamster

Warm ambient temperature (38°C) provided daily for one hr induced time-dependent changes in body weight and fat stores in the Syrian hamster. In animals held on 10-hr daily photoperiods and room temperature (23°C), daily one-hour thermopulses at 8 and 20 hr after light onset stimulated increases in body weights and indices of body fat storage. Abdominal fat pad weights of these groups were twice those of untreated controls after 17 and 28 days of thermoperiodic treatments. On the other hand, daily thermopulses were completely ineffective at 0 and 16 hr after light onset. These results demonstrate that body fat stores may be influenced by a temporal interaction of environmental stimuli and implicate underlying circadian mechanisms in the regulation of body fat.

Body fat regulation during pregnancy and lactation: the roles of diet and insulin.

Body fat regulation during pregnancy and lactation: the roles of diet and insulin.

Recovery of Body Weight from Below “Set Point” in Mature Female Rats

In this study we determined the time course of changes in body composition and of serum concentrations of some hormones in mature rats returning to “set point” following weight loss. Groups of six female rats were fed ad libitum for 10 days. Carcass composition of one group was determined. A control group continued to eat ad libitum. The others were restricted to 5 g per rat per day for 22 days. Carcass composition of groups of rats was determined after 0, 2, 6, 13 and 20 days of refeeding. Of 60 g of body weight lost during restriction, 21 g were fat and 12 g were protein. The fat was replaced by the sixth day of refeeding. Protein and body weight were recovered by the thirteenth day. Calculated efficiency of energy retention was increased until body fat was replete. This was not due to a decrease in metabolism of brown fat, measured in vitro. Serum thyroxine (T4), L-3,3′,5′-triiodothyronine (rT3), insulin, corticosterone and free fatty acids did not change with body composition. T3 (L-3,3′,5-triiodothyronine) decreased in restricted rats and returned to control levels when body weight, protein and food intake had been restored. These results do not support the concept that body weight is controlled by regulating body fat content.

The metabolic basis of dual periodicity of feeding in rats

AbstractThis article examines how the depletion and replenishment of various energy stores give rise to periodic eating and how constant body-energy levels are maintained over time.Measures of the energy expended throughout the 24-hour feeding pattern in rats indicate that two different energy stores (one of small capacity and one of large) determine two superimposed feeding periodicities: one from meal to meal (prandial), the other from day to night (nycthemeral). The article reviews how experimental overrepletion or overdepletion of gastrointestinal content, blood glucose, or body fats affect food intake. These data suggest that gastrointestinal content determines both meal size and meal-to-meal periodicity. Other evidence indicates that glucose uptake rate in tissues, which is modulated by fat synthesis and fat mobilization, affects the periodic onset of feeding and the difference between nocturnal and diurnal postprandial satiety.There follows an examination of the neuroendocrine bases for the interacting mechanisms governing energy input and output balance and of the role of the ventromedial hypothalamus in body-fat regulation and the lateral hypothalamus in feeding.

Energy Balances in Obese Mice

According to most existing theories, the regulation of energy balance is achieved by control of energy intake. This study was undertaken to find out whether there was control of energy output as well. Food intake, energy balance and the feed efficiency of weanling female mice made obese with injections of gold-thioglucose and monosodium glutamate indicate that the obesity is primarly due to an increased energetic efficiency, and suggest that the hypothalamus plays a role in controlling energy output. In the case of treatment with MSG, a relative obesity was observed, i.e. an increase in body fat without any change in body weight. This indicates that the CNS centres for the regulation of body weight and body fat are probably not the same. It is suggested that MSG obesity will be a suitable model for comparative studies of body weight and the regulation of fat content. It is concluded that chemically induced obesity is due more to a lower metabolic rate than to an elevated food intake.

INTERRELATIONS BETWEEN LEPTIN &amp; OBESITY

Objective: Excess body weight is the sixth most important risk factor contributing to the overall burden ofdisease worldwide. The circulating leptins have been found to play a vital role in the regulation of appetite,glucose homeostasis and body fat. Therefore, this study was designed to measure serum leptin and insulinresistance in non obese and obese young adults and to correlate them with obesity parameters: body massindex, waist circumference, waist-to-hip ratio and metabolic indices.Methods: A total of 43 non- obese subjects, 20 male and 23 female aged 20- 25 years and 46 obese subjects,25 male and 21 female with age 28- 37 years were studied. All subjects selected for study were normotensiveand non-diabetic. Variables measured were Body Mass Index (BMI), waist to hip ratio(WHR), bloodpressure, serum leptin, insulin, fasting blood glucose, oral glucose tolerance test (OGTT), and lipid profile.Results: Serum leptin was significantly higher in females than males 8.8 ± 2.10 SEM and 2.2 ± 0.26 ng/mlSEM respectively in non-obese.As well, Serum leptin was significantly higher in females than males 23.0 ±3.98 SEM and 12.5 ± 2.24 ng/ml SEM respectively in obese group. Serum leptin was significantly higher inobese males, and obese females compared to non- obese subjects. Serum leptin significantly, and positivelycorrelated with BMI (r = 0.440), hip circumference (r =0.425), insulin (r = 0.334), and homeostasis Model ofAssessment - Insulin Resistance (HOMA-IR)r= 0.334 whereas HOMA-IR positively correlated with BMI,waist Circumference, fasting insulin, fasting blood glucose, triglycerides (TG), TG/HDL-Cholesterol ratioand negatively correlated with HDL-Cholesterol.Conclusions: Serum leptin levels increase with obesity, and are higher in females in both non-obese andobese individuals. Serum leptin significantly correlated with hip circumference. Increased serum leptin,especially in obese subjects, should be taken as a warning sign of energy imbalance, poor diet,hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are stronglyassociated with cardiovascular diseases and type 2 diabetes. &#x0D; Key words: Anthropometry, body mass index, insulin resistance, leptin, obesity,

Dietary obesity in rats: influence of diet, weight, age, and sex on body composition.

Dietary obesity in rats: influence of diet, weight, age, and sex on body composition.