Regulation Of Adipose Tissue Mass Research Articles

Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis.

Obesity is characterized by an expansion of white adipose tissue mass that results from an increase in the size and the number of adipocytes. However, the mechanisms responsible for the formation of adipocytes during development and the molecular mechanisms regulating their increase and maintenance in adulthood are poorly understood. Here, we report the use of leptin-luciferase BAC transgenic mice to track white adipose tissue (WAT) development and guide the isolation and molecular characterization of adipocytes during development using DNA microarrays. These data reveal distinct transcriptional programs that are regulated during murine WAT development in vivo. By using a de novo cis-regulatory motif discovery tool (FIRE), we identify two early gene clusters whose promoters show significant enrichment for NRF2/ETS transcription factor binding sites. We further demonstrate that Ets transcription factors, but not Nrf2, are regulated during early adipogenesis and that Ets2 is essential for the normal progression of the adipocyte differentiation program in vitro. These data identify ETS2 as a functionally important transcription factor in adipogenesis and its possible role in regulating adipose tissue mass in adults can now be tested. Our approach also provides the basis for elucidating the function of other gene networks during WAT development in vivo. Finally these data confirm that although gene expression during adipogenesis in vitro recapitulates many of the patterns of gene expression in vivo, there are additional developmental transitions in pre and post-natal adipose tissue that are not evident in cell culture systems.

Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis

Obesity is characterized by an expansion of white adipose tissue mass that results from an increase in the size and the number of adipocytes. However, the mechanisms responsible for the formation of adipocytes during development and the molecular mechanisms regulating their increase and maintenance in adulthood are poorly understood. Here, we report the use of leptin-luciferase BAC transgenic mice to track white adipose tissue (WAT) development and guide the isolation and molecular characterization of adipocytes during development using DNA microarrays. These data reveal distinct transcriptional programs that are regulated during murine WAT development in vivo. By using a de novo cis-regulatory motif discovery tool (FIRE), we identify two early gene clusters whose promoters show significant enrichment for NRF2/ETS transcription factor binding sites. We further demonstrate that Ets transcription factors, but not Nrf2, are regulated during early adipogenesis and that Ets2 is essential for the normal progression of the adipocyte differentiation program in vitro. These data identify ETS2 as a functionally important transcription factor in adipogenesis and its possible role in regulating adipose tissue mass in adults can now be tested. Our approach also provides the basis for elucidating the function of other gene networks during WAT development in vivo. Finally these data confirm that although gene expression during adipogenesis in vitro recapitulates many of the patterns of gene expression in vivo, there are additional developmental transitions in pre and post-natal adipose tissue that are not evident in cell culture systems.

The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications

Obesity and vitamin D deficiency have both been recognized as major public health issues worldwide, and there is growing evidence that they are related, although the cause-effect relationship remains unclear. Could obesity be contributing to low circulating 25-hydroxyvitamin D concentrations? Alternatively, could low vitamin D status predispose to obesity? In this review, the relationship between low circulating 25-hydroxyvitamin D and obesity, and possible underlying reasons from both perspectives, is presented. One potential mechanism by which obesity could contribute to low serum 25-hydroxyvitamin D is adipose sequestration of vitamin D. On the other hand, adipose tissue has both the vitamin D receptor and the ability to synthesize 1,25-dihydroxyvitamin D, and there is evidence that vitamin D may regulate adipose tissue mass, differentiation and metabolism in ways that might contribute to obesity. Of particular interest, vitamin D deficiency is common both before and after bariatric surgery, and is often difficult to treat, particularly with the more malabsorptive procedures. Additional research is needed to elucidate the complex and multifaceted factors underlying the association between low circulating 25-hydroxyvitamin D and obesity, and to identify optimal treatment approaches in obese individuals and in bariatric surgical patients both before and after surgery.

Mate Tea (Ilex paraguariensis) Promotes Satiety and Body Weight Lowering in Mice: Involvement of Glucagon-Like Peptide-1

We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. GLP-1 is a peptide signal generated by the gastrointestinal tract, which regulates appetite and influences BW, whereas leptin is an afferent signal from the periphery to the brain in a homeostatic feedback loop that regulates adipose tissue mass, thus leading to decreased appetite and FI and increased energy expenditure. Chronic administration of mate (50, 100 mg/kg) for 3 weeks significantly reduced FI, BW, and ameliorated blood fats, liver fats, and adipose tissue. Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.

Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Tumor necrosis factor-α (TNF-α) is a key regulator of adipose tissue mass, but mechanisms underlying this effect have not been fully elucidated. We found that exposure to TNF-α caused a significant decrease in the number of adipocytes, but not preadipocytes. Subsequent experiments revealed that TNF-α selectively deleted adipocytes through induction of apoptosis. Following exposure to TNF-α, rapid activation of nuclear factor-κB (NF-κB) was observed only in preadipocytes, but not in adipocytes. Inhibition of NF-κB rendered preadipocytes susceptible to TNF-α-induced apoptosis, suggesting that different activity of NF-κB is the determinant for the distinct apoptotic responses. During adipocyte differentiation, expression and activity of peroxisome proliferator-activated receptor-γ (PPARγ) were upregulated. Treatment of preadipocytes with a PPARγ agonist attenuated NF-κB activation and rendered the cells vulnerable to TNF-α-induced apoptosis. Conversely, treatment of adipocytes with a PPARγ antagonist enhanced NF-κB activation and conferred resistance to TNF-α-induced apoptosis, suggesting involvement of PPARγ in the suppression of NF-κB in adipocytes. We also found that, following differentiation, expression and activity of CCAAT/enhancer binding protein (C/EBP), especially C/EBPα and C/EBPβ, were upregulated in adipocytes. Overexpression of individual C/EBPs significantly inhibited activation of NF-κB in preadipocytes. Furthermore, transfection with siRNA for C/EBPα or C/EBPβ enhanced activity of NF-κB in adipocytes, suggesting that C/EBP is also involved in the repression of NF-κB in adipocytes. These results suggested novel mechanisms by which TNF-α selectively deletes adipocytes in the adipose tissue. The C/EBP- and PPARγ-mediated suppression of NF-κB may contribute to TNF-α-related loss of adipose tissue mass under certain pathological situations, such as cachexia.

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.

Leptin at 14 y of age: an ongoing story

The cloning of the ob gene and its gene product leptin has led to the elucidation of a robust physiologic system that maintains constancy of fat stores. Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance. Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored. When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass.

DNA Extraction Methods Used in Leptin’s Identification from Buffolo Milk

Leptin is a 16 kDa protein hormone mainly but not exclusively produced and secreted by adipose tissue, which functions as the afferent signal in a feedback loop regulating adipose tissue mass. The progress in animal breeding may be improved by combining traditional performance data with molecular genetic information on quantitative loci in selection index (Buchanan F.C. et al.,2003) The main purpose of this study was to compare different DNA extraction methods needed in PCR. By PCR we can identify leptin’s allele responsible for the quality and production traits of milk. The study material was represented by 30 samples of blood, milk and colostrums taken from buffalos from Salaj and Cluj County. The DNA extraction from blood was done from the leukocytes layer revealed after blood’s coagulation, using the standard protocol written in the paper. The DNA quantity values obtained ranged between 18.9 – 198.4 ng/ µL, and the DNA purity values between 1.07 – 1.76 wavelength 260/280. The DNA extraction from milk’s somatic cells was done using two methods: the rapid method of extraction with PBS, and the classic method. The DNA quantity values obtained through these methods ranged between 14.2 – 156.8 ng/ μL, and the purity values between 1-2 wave lengths 260/280. The DNA quantity and purity values obtained by these three methods were statistically analysed using the ANOVA test and the p values were 0.04476 and 0.02588 which means that there are no significant differences between them. The DNA extraction method from blood can be replaced with succes by these methods of extraction from milk, given the fact that these methods do not imply such a laborious work and uneccessary stress to the buffalos.

Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass

IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way regulate adipose tissue mass. The relation between skeletal muscle IL-15 mRNA expression, plasma IL-15, and adipose tissue mass was studied in 199 humans divided into four groups on the basis of obesity and type 2 diabetes. Furthermore, using a DNA electrotransfer model, we assessed the effect of IL-15 overexpression in skeletal muscle of mice. In humans, multiple regression analysis showed a negative association between plasma IL-15 and total fat mass (P<0.05), trunk fat mass (P<0.01), and percent fat mass (P<0.05), independent of type 2 diabetes. Negative associations were also found between muscle IL-15 mRNA and obesity parameters. IL-15 overexpression in skeletal muscle of mice reduced trunk fat mass but not sc fat mass. Our results indicate that IL-15 may be a regulator of trunk fat mass.

The endocannabinoid-CB receptor system: a new player in the brain-gut-adipose field

The 1990's have witnessed the discovery of the 'endocannabinoid-cannabinoid (CB) receptor (ECBR) system' consisting of specific receptors (CB1 and CB2), at least 3 endogenous ligands (anandamide, 2-arachidonyl glycerol and noladin ether) and their enzymes. Subsequently, a series of discoveries were made on the involvement of the ECBR system in many physiological functions including immunity, inflammation, neurotoxicity and neurotrauma, epilepsy, depression and stress, appetite, food intake and energy homeostasis, cardiovascular regulation, reproduction, and bone remodeling. The brain-gut-adipose axis regulates digestive processes, food ingestion and energy balance and is closely associated with hormonal regulation by the hypothalamic-pituitary-adrenal stress axis and by the mesolimbic reward It is proposed to call these interfacing systems the control system. ECBR presence in brain, gastrointestinal as well as adipose tissue explains its role in food intake, digestion and the regulation of adipose tissue mass. Moreover, the ECBR system's involvement in stress and emotional processing, makes it eminently suited to be (one of) the principle players in the alimentary control The ECBR system is present during the early embryonal and postnatal stages and we have discovered endocannabinoids in maternal milk. The ECBR system seems to be of critical value for newborn milk ingestion and suckling. Ghrelin, an orexigenic gastric hormone, exerts many effects similar to those of endocannabinoids. Therefore this review will compare some of the functions and anatomy of ghrelin and endocannabinoids. It is concluded that (i) the ECBR system is a major mediator between the brain and the alimentary system, and possibly, the adipose tissue, (ii) the role of the ECBR system in adult regulation of food processing is a remnant of its critical role for the initiation of feeding in the newborn, and (iii) the pervasive influence of the ECBR system in alimentary control make it a highly suitable target for therapeutic developments for pathophysiological conditions such as inflammatory bowel disease, irritable bowel syndrome, gastric ulcers, nausea, anorexia and failure-to-thrive. Biomedical Reviews 2006; 17: 23-42.

Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow

The accumulation of fat cells (adipocytes) in bone marrow is now thought to be a factor contributing to age-related bone loss. Women with osteoporosis have higher numbers of marrow adipocytes than women with healthy bone, and bone formation rate is inversely correlated with adipocyte number in bone tissue biopsies from both men and women. Adipogenic differentiation of bone marrow stromal cells increases with age, but the factors regulating populations of mature adipocytes are not well understood. Leptin is thought to regulate adipose tissue mass via its receptors in the ventromedial hypothalamus (VMH). We have therefore tested the hypothesis that stimulation of leptin receptors in the VMH regulates adipocyte number in bone marrow. Results indicate that unilateral twice-daily injections of leptin into the rat VMH for only 4 or 5 days cause a significant reduction in the number of adipocytes in peripheral fat pads and bone marrow and indeed eliminate adipocytes almost entirely from bone marrow of the proximal tibia. Osteoblast surface is not affected with leptin treatment. Apoptosis assays performed on bone marrow samples from control and treated rats have revealed a significant increase in protein concentration of the apoptosis marker caspase-3 with leptin treatment. We conclude that stimulation of leptin receptors in the VMH significantly decreases the adipocyte population in bone marrow, primarily through apoptosis of marrow adipocytes. Elimination of marrow adipocytes via this central pathway may represent a useful strategy for the treatment and prevention of osteoporosis.

Vitamin A supplementation induces adipose tissue loss through apoptosis in lean but not in obese rats of the WNIN/Ob strain

Vitamin A is a known regulator of adipose tissue growth. In this paper, we report the possible role of dietary vitamin A supplementation in the regulation of adipose tissue mass, using a novel obese rat model of the WNIN/Ob strain developed at the National Centre for Laboratory Animal Sciences of the National Institute of Nutrition, India. Twenty-four male lean and obese rats of the WNIN/Ob strain were broadly divided into two groups at 7 months of age; each group was subdivided into two subgroups consisting of six lean and six obese rats and they were given diets containing either 2.6 mg or 129 mg vitamin A/kg diet for 2 months. Feeding a high but non-toxic dose of vitamin A (129 mg/kg diet) resulted in a significant reduction in the adiposity index and retroperitoneal white adipose tissue (RPWAT) weight in obese rats while a marginal reduction was observed in lean rats. Further, this treatment resulted in a significantly increased RPWAT apoptotic index and Bax protein expression and a decreased expression of Bcl2 in the lean rats. However, no such changes were observed in the RPWAT of the obese rats subjected to identical treatment. Thus, our data suggests that chronic dietary vitamin A supplementation at a high dose effectively regulates adipose tissue mass both in the lean and obese phenotypes of the WNIN/Ob rat strain, perhaps through different mechanisms.

Fibroblast Growth Factor 1

Obesity, with its related problems, is recognized as the fastest growing disease epidemic facing the world, yet we still have limited insight into the regulation of adipose tissue mass in humans. We have previously shown that adipose-derived microvascular endothelial cells (MVECs) secrete a factor(s) that increases proliferation of human preadipocytes. We now demonstrate that coculture of human preadipocytes with MVECs significantly increases preadipocyte differentiation, evidenced by dramatically increased triacylglycerol accumulation and glycerol-3-phosphate dehydrogenase activity compared with controls. Subsequent analysis identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by MVECs. Expression of FGF-1 was demonstrated in MVECs but not in preadipocytes, while preadipocytes were shown to express FGF receptors 1-4. The proliferative effect of MVECs on human preadipocytes was blocked using a neutralizing antibody specific for FGF-1. Pharmacological inhibition of FGF-1 signaling at multiple steps inhibits preadipocyte replication and differentiation, supporting the key adipogenic role of FGF-1. We also show that 3T3-L1 cells, a highly efficient murine model of adipogenesis, express FGF-1 and, unlike human preadipocytes, display no increased differentiation potential in response to exogenous FGF-1. Conversely, FGF-1-treated human preadipocytes proliferate rapidly and differentiate with high efficiency in a manner characteristic of 3T3-L1 cells. We therefore suggest that FGF-1 is a key human adipogenic factor, and these data expand our understanding of human fat tissue growth and have significant potential for development of novel therapeutic strategies in the prevention and management of human obesity.

Leptin levels in the acute stage of ulcerative colitis.

Leptin, a recently discovered protein, acts as a hormonal feedback signal in regulating adipose tissue mass via hypothalamic mechanisms. Inflammatory bowel disease is often associated with anorexia and weight loss. The aim of the present study was to investigate serum leptin levels during the time course of the acute phase of ulcerative colitis (UC) and to evaluate whether leptin leads to anorexia and bodyweight loss in these patients. Serum leptin levels of 29 male patients with acute UC and 17 healthy controls with similar age, sex and body mass index (BMI) were measured. Erythrocyte sedimentation rate (ESR), BMI, serum albumin and C-reactive protein concentrations, and white blood cell counts were determined. A significant increase in serum leptin levels was found in patients with acute UC when compared with controls (5.89 +/- 2.06 ng/mL and 3.64 +/- 1.69 ng/mL, respectively; p = 0.001). There was no correlation between leptin levels and BMI. Our findings in the acute stage of UC suggest that increased serum leptin levels may contribute to anorexia and weight loss. However, an inappropriate increase in leptin levels is independent of body mass in acute UC, and we believe that other factors may be involved in inflammation-induced increases in leptin levels.

Dehydroepiandrosterone up-regulates resistin gene expression in white adipose tissue

Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in human blood, is considered to be one of fat-reducing hormones. However, the molecular mechanisms underlying DHEA mode of action in obesity has not been fully clarified. The pivotal role in the maintenance of cellular lipid and energy balance is played by peroxisome proliferator-activated receptor α (PPARα) which acts as transcriptional activator of numerous genes encoding enzymes involved in fatty acid catabolism. Lately published papers suggest that resistin, a low molecular-weight protein produced by adipose tissue, may act as an inhibitor of adipocyte differentiation and could regulate adipose tissue mass. Recent studies have established that the promoter region of the resistin gene contains several putative PPAR response elements. Since DHEA has been characterized as a peroxisome proliferator able to induce hepatic genes through PPARα, we hypothesised that DHEA might affect PPARα and, subsequently, resistin gene expression in adipose tissue. In order to test this hypothesis, an experiment was performed comparing PPARα and resistin gene expression in white adipose tissue (WAT) of male Wistar rats fed standard or DHEA-supplemented (0.6% (w/w)) diet for 2 weeks. DHEA administration to the rats induced PPARα and resistin gene expression in WAT (3- and 2.25-fold, respectively; as determined by real-time reverse transcription-polymerase chain reaction (RT-PCR)); reduced body weight, epididymal adipose tissue mass and decreased serum leptin levels. We propose that DHEA may impact on the transcription of resistin gene through a mechanism involving PPARα and that an elevated resistin level may lead to an inhibition of adipogenesis and a decrease in adipose tissue mass.

Inhibition of death-receptor mediated apoptosis in human adipocytes by the insulin-like growth factor I (IGF-I)/IGF-I receptor autocrine circuit.

Adipose tissue mass is reflected by the volume and the number of adipocytes and is subject to homeostatic regulation involving cell death mechanisms. In this study we have investigated the mechanisms of apoptosis in human preadipocytes and adipocytes that may play a role in the regulation of adipose tissue mass. We found that death receptors (CD95, TNF-related apoptosis-inducing ligand receptors 1 and 2, and TNF receptor 1) are expressed in human fat cells and that apoptosis can be induced by specific ligands. Sensitivity to apoptosis could be stimulated by an inhibitor of biosynthesis. In addition, inhibition of auto-/paracrine action of IGF-I dramatically sensitizes human adipocytes for death ligand-induced apoptosis. Phosphoinositide 3-kinase and, to a weaker extent, p38 MAPK are involved in IGF-I-mediated survival. IGF-I protects human fat cells from apoptosis by maintaining the expression of antiapoptotic proteins, Bcl-x(L) and Fas-associated death domain-like IL-1-converting enzyme inhibitory protein. In conclusion, we identified mechanisms of apoptosis induction in human fat cells. We furthermore demonstrate that human fat cells protect themselves from apoptosis by IGF-I in an auto-/paracrine manner.

Selective adipose tissue ablation by localized, sustained drug delivery.

The reduction of adipose depots is widely considered to be the optimal approach to limit pathologies associated with obesity. While many current antiobesity strategies are centered on regulating satiety, these approaches typically attempt an overall weight loss and are unable to target distinct adipose depots specifically associated with disease risk. The authors report a novel therapeutic modality utilizing localized and sustained delivery of drugs to provide for the selective ablation of adipose tissue. Using the epididymal fat pad of Sprague-Dawley rats as a model, they injected into the tissue poly(lactide-co-glycolide) microspheres encapsulating tumor necrosis factor-alpha, a well-known regulator of adipose tissue mass. The utility of this approach was investigated in vivo by measuring the fat pad mass relative to the contralateral control within the same animal (n = 4 at each time point) and in vitro by measuring apoptosis in adipose organ cultures. The authors demonstrated control over the localization of tumor necrosis factor-alpha by performing blood analysis. This is the first report of localized drug delivery for adipose tissue ablation, and these results indicate the potential utility of the general tissue ablation approach for treatment of numerous pathologies.

Tumour necrosis factor alpha: a key regulator of adipose tissue mass.

In addition to its established role in the immune system, tumour necrosis factor alpha (TNFalpha) exerts complex regulatory actions on adipose tissue. TNFalpha is produced in and secreted by the adipocyte and thus is in a position to exert a paracrine and/or autocrine role within adipose tissue. TNFalpha affects many aspects of adipocyte function, from adipocyte development to lipid metabolism. Bringing together all of these diverse actions, TNFalpha appears to play a general role in reducing adipose tissue mass. Dysregulation of TNFalpha production and/or action could be one facet in the development of cachexia and obesity, as well as associated metabolic disorders such as insulin resistance.

Plasma leptin levels in children with cyanotic and acyanotic congenital heart disease and correlations with growth parameters

Background: Leptin has been shown to be an integral component of energy homeostasis and regulation of body weight. Leptin regulates adipose tissue mass and correlates with the fat mass, however the circulating levels are altered by energy intake. Research on the physiological function of leptin has primarily focused on its role in the pathogenesis of obesity. However, its role in the negative energy imbalance is unclear. Increased energy expenditure is a primary factor in the reduced growth in infants with cyanotic congenital heart disease. The objective of this study was to examine the possible role of leptin on growth and nutrition in children with cyanotic and acyanotic congenital heart disease. Methods and Results: In this study, plasma leptin levels, nutritional and growth status were evaluated in 28 cyanotic and 20 acyanotic patients with congenital heart disease. Although standard deviation (S.D.) of height ( P<0.01), mid arm circumference (MAC) ( P<0.001) and body mass index (BMI) ( P<0.05) were significantly low in cyanotic group, plasma leptin levels were similar. Energy intake was high in cyanotic group. In both cyanotic and acyanotic group, plasma leptin levels were correlated with BMI ( r: 0.388, P<0.05 and r: 0.789, P<0.001, respectively). In addition, leptin levels were significantly correlated with the height ( r: 0.415, P<0.05), MAC ( r: 0.482, P<0.05) and BMI ( r: 0.377, P<0.05) S.D. in cyanotic subjects. Conclusions: Our results suggest that the leptin regulating axis is intact in cyanotic patients and leptin does not contribute to the cachexia of cyanotic heart disease.

Exogenous leptin controls the development of the small intestine in neonatal piglets.

Leptin, a hormone produced and secreted by adipose tIssue, muscles and stomach, is involved in the regulation of adipose tIssue mass, food intake and body weight in neonatal animals. It is also produced in the mammary glands and secreted into the colostrum and milk. Since leptin receptors are widely distributed in the small intestine mucosa, the aim of the present study was to investigate the effect of exogenous leptin on the development of the small intestine in neonatal piglets. Male neonatal piglets were fed with sow's milk or artificial milk formula. Every 8 h the latter received either vehicle or leptin (2 or 10 microg/kg body weight). The animals were either killed after 6 days of treatment and the small intestine sampled for histology and brush border enzyme activities or were tested for marker molecule (Na-fluorescein and BSA) absorption in vivo. Feeding milk formula slowed the maturation of small intestinal mucosa compared with feeding sow's milk. However, after leptin treatment the length of the small intestine was increased, and intestinal villi length, but not crypt size, was reduced compared with controls. The mitotic index was increased and the percentage of vacuolated enterocytes was reduced in the entire small intestine. Enterocyte brush border protease and lactase activities were reduced in the jejunum. Na-fluorescein marker molecule absorption did not change but that of BSA was reduced 3.8-fold. In conclusion, exogenous leptin administered in physiological doses reversed the maturation of the small intestinal mucosa to the range found in sow-reared piglets.