scholarly journals High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1477
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Jong Yup Sa ◽  
Rebecca Simonian ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Leptin Receptor ◽  
Liver Weight ◽  
Female Offspring ◽  
Mature Female ◽  
Cytokine Signaling ◽  
Light Cycle ◽  
Energy Regulation

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.

scholarly journals High 5-Methyletetrahydrofolate and Folic Acid Gestational Diets Differ on Leptin-Dependent Hypothalamic Genes Regulating Food Intake in Female Offspring

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1322-1322
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
G Harvey Anderson
Keyword(s):  
Folic Acid ◽  
Food Intake ◽  
Gaba Receptors ◽  
Female Offspring ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
High Dose ◽  
Regulatory Pathways ◽  
Plasma Leptin ◽  
Energy Regulatory

Abstract Objectives While the replacement of folic acid (FA) with the bioactive folate form 5-methyltetrahydrofolate (MTHF) is gaining popularity, a comparison of their effects during pregnancy is limited. In a comparison of maternal intakes of FA and MTHF at recommended or high (5X) doses in Wistar rat dams, we found that dams fed 5X MTHF gained &gt; 70% more weight and ate 8% more food to 19-weeks post weaning (PW) than those fed the high FA diet (Nutrients. 2021;13:48). However, both high dose diets resulted in dysregulation of leptin and central energy regulatory systems. The objective of this study was to compare the effect of gestational FA and MTHF diets on metabolic response and leptin-dependent hypothalamic energy-regulatory genes in the brain of their female offspring. Methods Pregnant Wistar rats were fed an AIN-93G diet with 1X recommended (2mg/kg diet) or 5X FA or equimolar MTHF. At weaning, female offspring were fed a high-fat diet until 19-weeks PW. Body weight, food intake, adiposity, plasma leptin, and gene expression of leptin signaling and related candidate genes in the hypothalamus were measured. Results Similar to the mothers, the 5X-MTHF gestational diet resulted in offspring with higher weight (&gt;15%, P &lt; 0.01) independent of visceral adiposity, and higher food intake (8% P &lt; 0.01) compared to those born to dams fed the 5X-FA, but not from the 1X folate diets. Both 5X diets led to higher plasma leptin at birth (60%, P &lt; 0.05) and at 19-weeks PW (40%, P &lt; 0.01) and up-regulated hypothalamic mRNA of the downstream leptin signalling gene, signal transducer and activator of transcription-3 (Stat3). However, only 5X-MTHF offspring had lower expression of leptin receptor (Ob-rB) and higher expression of suppressor of cytokine signaling-3 (Socs-3), an inhibitor of leptin signalling and indicator of central leptin resistance. In contrast, 5X-FA offspring had higher expression (&gt;1.5-fold, P &lt; 0.01) of dopamine and GABA- receptors which are targets of leptin and associated with feeding inhibition and hyperactivity. Conclusions Folate form and dose during pregnancy affects long-term programming of leptin dependent hypothalamic regulatory pathways in female offspring. Unfavorable differences in response to FA and MTHF were seen at the higher doses, thus neither should be consumed at high intakes. Funding Sources CIHR-INMD; EP by NSERC-CGS.

scholarly journals Increased Hypothalamic Signal Transducer and Activator of Transcription 3 Phosphorylation after Hindbrain Leptin Injection

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marieke Ruiter ◽  
Patricia Duffy ◽  
Steven Simasko ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Leptin Receptor ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Solitary Tract ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Reduction of food intake and body weight by leptin is attributed largely to its action in the hypothalamus. However, the signaling splice variant of the leptin receptor, LRb, also is expressed in the hindbrain, and leptin injections into the fourth cerebral ventricle or dorsal vagal complex are associated with reductions of feeding and body weight comparable to those induced by forebrain leptin administration. Although these observations suggest direct hindbrain action of leptin on feeding and body weight, the possibility that hindbrain leptin administration also activates the Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in the hypothalamus has not been investigated. Confirming earlier work, we found that leptin produced comparable reductions of feeding and body weight when injected into the lateral ventricle or the fourth ventricle. We also found that lateral and fourth ventricle leptin injections produced comparable increases of STAT3 phosphorylation in both the hindbrain and the hypothalamus. Moreover, injection of 50 ng of leptin directly into the nucleus of the solitary tract also increased STAT3 phosphorylation in the hypothalamic arcuate and ventromedial nuclei. Increased hypothalamic STAT3 phosphorylation was not due to elevation of blood leptin concentrations and the pattern of STAT3 phosphorylation did not overlap distribution of the retrograde tracer, fluorogold, injected via the same cannula. Our observations indicate that even small leptin doses administered to the hindbrain can trigger leptin-related signaling in the forebrain, and raise the possibility that STAT3 phosphorylation in the hypothalamus may contribute to behavioral and metabolic changes observed after hindbrain leptin injections.

scholarly journals Changes in Expression of the Genes for the Leptin Signaling in Hypothalamic-Pituitary Selected Areas and Endocrine Responses to Long-Term Manipulation in Body Weight and Resistin in Ewes

2020 ◽  
Vol 21 (12) ◽  
pp. 4238
Author(s):  
Dorota Anna Zieba ◽  
Weronika Biernat ◽  
Malgorzata Szczesna ◽  
Katarzyna Kirsz ◽  
Justyna Barć ◽  
...  
Keyword(s):  
Body Weight ◽  
Leptin Receptor ◽  
Fat Body ◽  
Density Lipoprotein ◽  
Reproductive Hormones ◽  
Leptin Resistance ◽  
Nonesterified Fatty Acid ◽  
Cytokine Signaling ◽  
Leptin Signaling

Both long-term undernutrition and overnutrition disturb metabolic balance, which is mediated partially by the action of two adipokines, leptin and resistin (RSTN). In this study, we manipulated the diet of ewes to produce either a thin (lean) or fat (fat) body condition and investigated how RSTN affects endocrine and metabolic status under different leptin concentrations. Twenty ewes were distributed into four groups (n = 5): the lean and fat groups were administered with saline (Lean and Fat), while the Lean-R (Lean-Resistin treated) and Fat-R (Fat-Resistin treated) groups received recombinant bovine resistin. Plasma was assayed for LH, FSH, PRL, RSTN, leptin, GH, glucose, insulin, total cholesterol, nonesterified fatty acid (NEFA), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Expression levels of a suppressor of cytokine signaling (SOCS-3) and the long form of the leptin receptor (LRb) were determined in selected brain regions, such as the anterior pituitary, hypothalamic arcuate nucleus, preoptic area and ventro- and dorsomedial nuclei. The results indicate long-term alterations in body weight affect RSTN-mediated effects on metabolic and reproductive hormones concentrations and the expression of leptin signaling components: LRb and SOCS-3. This may be an adaptive mechanism to long-term changes in adiposity during the state of long-day leptin resistance.

scholarly journals Role of SOCS3 in POMC neurons in metabolic and cardiovascular regulation

2019 ◽  
Vol 316 (4) ◽  
pp. R338-R351 ◽  
Author(s):  
Zhen Wang ◽  
Jussara M. do Carmo ◽  
Alexandre A. da Silva ◽  
Kandice C. Bailey ◽  
Nicola Aberdein ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Food Intake ◽  
Stress Test ◽  
Control Diet ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Male And Female ◽  
Air Jet ◽  
And Control

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling. We previously showed that the chronic effects of leptin on blood pressure (BP) and glucose regulation are mediated by stimulation of proopiomelanocortin (POMC) neurons. In this study we examined the importance of endogenous SOCS3 in POMC neurons in control of metabolic and cardiovascular function and potential sex differences. Male and female SOCS3flox/flox/POMC-Cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were studied during a control diet (CD) or a high-fat diet (HFD) and during chronic leptin infusion. Body weight was lower in male and female SOCS3flox/flox/POMC-Cre than control mice fed the CD, despite similar food intake. Male SOCS3flox/flox/POMC-Cre mice exhibited increased energy expenditure. BP and heart rate were similar in male and female SOCS3flox/flox/POMC-Cre and control mice fed the CD. HFD-fed male and female SOCS3flox/flox/POMC-Cre mice showed attenuated weight gain. HFD-induced elevations in baseline BP and BP responses to an air-jet stress test were greater in female SOCS3flox/flox/POMC-Cre than control mice. Chronic leptin infusion produced similar responses for food intake, body weight, oxygen consumption, blood glucose, BP, and heart rate in all groups. Thus SOCS3 deficiency in POMC neurons influences body weight regulation in the setting of CD and HFD and differentially affects BP and energy balance in a sex-specific manner but does not amplify the dietary, glycemic, or cardiovascular effects of leptin.

Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone

1993 ◽  
Vol 264 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
J. C. Byatt ◽  
N. R. Staten ◽  
W. J. Salsgiver ◽  
J. G. Kostelc ◽  
R. J. Collier
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Mature Female ◽  
Female Rats ◽  
Bovine Growth Hormone ◽  
Female Rat ◽  
Moisture Percentage

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.

Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia

2006 ◽  
Vol 290 (3) ◽  
pp. E591-E597 ◽  
Author(s):  
Nadine Simler ◽  
Alexandra Grosfeld ◽  
André Peinnequin ◽  
Michèle Guerre-Millo ◽  
André-Xavier Bigard
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Hypobaric Hypoxia ◽  
Leptin Receptor ◽  
Zucker Rats ◽  
Hypoxia Exposure ◽  
Obese Rats ◽  
Hypothalamic Neuropeptides

Exposure to hypoxia induces anorexia in humans and rodents, but the role of leptin remains under discussion and that of orexigenic and anorexigenic hypothalamic neuropeptides remains unknown. The present study was designed to address this issue by using obese (Leprfa/Leprfa) Zucker rats, a rat model of genetic leptin receptor deficiency. Homozygous lean (LeprFA/LeprFA) and obese (Leprfa/Leprfa) rats were randomly assigned to two groups, either kept at ambient pressure or exposed to hypobaric hypoxia for 1, 2, or 4 days (barometric pressure, 505 hPa). Food intake and body weight were recorded throughout the experiment. The expression of leptin and vascular endothelial growth factor (VEGF) genes was studied in adipose tissue with real-time quantitative PCR and that of selected orexigenic and anorexigenic neuropeptides was measured in the hypothalamus. Lean and obese rats exhibited a similar hypophagia (38 and 67% of initial values at day 1, respectively, P < 0.01) and initial decrease in body weight during hypoxia exposure. Hypoxia led to increased plasma leptin levels only in obese rats. This resulted from increased leptin gene expression in adipose tissue in response to hypoxia, in association with enhanced VEGF gene expression. Increased hypothalamic neuropeptide Y levels in lean rats 2 days after hypoxia exposure contributed to accounting for the enhanced food consumption. No significant changes occurred in the expression of other hypothalamic neuropeptides involved in the control of food intake. This study demonstrates unequivocally that altitude-induced anorexia cannot be ascribed to anorectic signals triggered by enhanced leptin production or alterations of hypothalamic neuropeptides involved in anabolic or catabolic pathways.

scholarly journals Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

2001 ◽  
pp. 529-539 ◽  
Author(s):  
MC Sugden ◽  
ML Langdown ◽  
MJ Munns ◽  
MJ Holness
Keyword(s):  
Body Weight ◽  
Protein Expression ◽  
Rat Model ◽  
Early Life ◽  
Leptin Receptor ◽  
Late Pregnancy ◽  
Female Offspring ◽  
Early Growth ◽  
Dexamethasone Treatment ◽  
Glucocorticoid Treatment

BACKGROUND: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. OBJECTIVE: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. DESIGN AND METHODS: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. RESULTS: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited significant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. CONCLUSIONS: The rat model of maternal dexamethasone treatment is established as a paradigm of 'programmed' hypertension in man. Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive fetal exposure to glucocorticoids could be a common early-life stimulus to the association between hyperinsulinaemia, hypertension and hyperleptinaemia often seen in individuals of low birthweight.

scholarly journals Leptin Sensitivity in the Developing Rat Hypothalamus

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6073-6082 ◽  
Author(s):  
A.-S. Carlo ◽  
M. Pyrski ◽  
C. Loudes ◽  
A. Faivre-Baumann ◽  
J. Epelbaum ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Primary Cultures ◽  
Cytokine Signaling ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Leptin Signaling ◽  
Leptin Sensitivity

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.

scholarly journals Restriction of food intake by PPP1R17-expressing neurons in the DMH

2021 ◽  
Vol 118 (13) ◽  
pp. e2100194118
Author(s):  
Caner Caglar ◽  
Jeffrey Friedman
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Protein Phosphatase ◽  
Leptin Receptor ◽  
Protein Phosphatase 1 ◽  
Regulatory Subunit ◽  
Similar Extent ◽  
Dorsomedial Hypothalamus ◽  
Increase Food Intake ◽  
Feeding Protocol

Leptin-deficient ob/ob mice eat voraciously, and their food intake is markedly reduced by leptin treatment. In order to identify potentially novel sites of leptin action, we used PhosphoTRAP to molecularly profile leptin-responsive neurons in the hypothalamus and brainstem. In addition to identifying several known leptin responsive populations, we found that neurons in the dorsomedial hypothalamus (DMH) of ob/ob mice expressing protein phosphatase 1 regulatory subunit 17 (PPP1R17) constitutively express cFos and that this is suppressed by leptin treatment. Because ob mice are hyperphagic, we hypothesized that activating PPP1R17 neurons would increase food intake. However, chemogenetic activation of PPP1R17 neurons decreased food intake and body weight of ob/ob mice while inhibition of PPP1R17 neurons increased them. Similarly, in a scheduled feeding protocol that elicits increased consumption, mice also ate more when PPP1R17 neurons were inhibited and ate less when they were activated. Finally, we found that pair-feeding of ob mice reduced cFos expression to a similar extent as leptin and that reducing the amount of food available during scheduled feeding in DMHPpp1r17 neurons also decreased cFos in DMHPpp1r17 neurons. Finally, these neurons do not express the leptin receptor, suggesting that the effect of leptin on these neurons is indirect and secondary to reduced food intake. In aggregate, these results show that PPP1R17 neurons in the DMH are activated by increased food intake and in turn restrict intake to limit overconsumption, suggesting that they function to constrain binges of eating.

scholarly journals Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

2021 ◽  
Author(s):  
Mohammed K. Hankir ◽  
Laura Rotzinger ◽  
Arno Nordbeck ◽  
Caroline Corteville ◽  
Annett Hoffmann ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Body Weight ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Leptin Receptor ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Sustained Weight Loss ◽  
Obese Rats

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of endogenous leptin action. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

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