scholarly journals Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

2016 ◽  
Vol 229 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Martina Holubová ◽  
Jana Zemenová ◽  
Barbora Mikulášková ◽  
Vladimíra Panajotova ◽  
Jiří Stöhr ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Obesity And Diabetes ◽  
Diabetes Diet ◽  
Zdf Rats

Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity, but are ineffective after peripheral application, owing to a limited ability to cross the blood–brain barrier. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of bothPrrp-knockout andPrrpreceptor-knockout mice. The aim of this study was to characterize the subchronic effect of a palmitoylated PrRP analog in two rat models of obesity and diabetes: diet-induced obese Sprague–Dawley rats and leptin receptor-deficient Zucker diabetic (ZDF) rats. In the rats with diet-induced obesity (DIO), a two-week intraperitoneal treatment with palmitoylated PrRP lowered food intake by 24% and body weight by 8%. This treatment also improved glucose tolerance and tended to decrease leptin levels and adipose tissue masses in a dose-dependent manner. In contrast, in ZDF rats, the same treatment with palmitoylated PrRP lowered food intake but did not significantly affect body weight or glucose tolerance, probably in consequence of severe leptin resistance due to a nonfunctional leptin receptor. Our data indicate a good efficacy of lipidized PrRP in DIO rats. Thus, the strong anorexigenic, body weight-reducing, and glucose tolerance-improving effects make palmitoylated PrRP an attractive candidate for anti-obesity treatment.

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.

Combination of Lorcaserin and GLP-1/glucagon Coagonist Improves Metabolic Dysfunction in Diet Induced-obese Mice

Drug Research ◽  
2020 ◽  
Vol 70 (08) ◽  
pp. 376-384
Author(s):  
Vishal Patel ◽  
Amit Joharapurkar ◽  
Samadhan Kshirsagar ◽  
Maulik Patel ◽  
Hardikkumar Savsani ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Body Weight Loss ◽  
Tolerance Test ◽  
Individual Therapy ◽  
Repeated Treatment ◽  
Obesity And Diabetes ◽  
Glucagon Receptors

Abstract Background Obesity and diabetes are major metabolic disorders that progress to severe morbidity and mortality. Neuroendocrine mechanisms controlling energy balance indicate that combination therapies are needed to sustain weight loss. Lorcaserin was one of the approved therapies for the treatment of obesity, which is recently withdrawn because a safety clinical trial, shows an increased occurrence of cancer. Coagonist of glucagon-like-peptide-1 (GLP-1) and glucagon receptors is a novel investigational therapy demonstrated to have both anti-obesity and anti-diabetic effect. Here, we investigated the effect of combination of lorcaserin and a GLP-1 and glucagon receptors coagonist in diet-induced obese (DIO) mice model. Methods The diet-induced obese C57BL/6J mice were used to assess acute and chronic effect of lorcaserin, coagonist of GLP-1and glucagon receptors and their combination on food intake, body weight, and biochemical parameters. Results In acute study, combination of lorcaserin and coagonist causes synergistic reductions in food intake and body weight. Repeated treatment of combination of lorcaserin and coagonist showed enhanced body weight loss over time, which is due to reduction in fat mass (subcutaneous, retroperitoneal, mesenteric and epididymal fat pad) compared to individual therapy. Also, suppression of locomotor activity seen with lorcaserin was not evident in combination with coagonist. No additive effect was observed in glucose tolerance (intraperitoneal glucose tolerance test or insulin tolerance test), serum lipids, hepatic lipids, and energy expenditure in combination group. Conclusion These data suggest that combination of lorcaserin and coagonist could be a better combination to induce body weight loss.

scholarly journals Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats

2015 ◽  
Vol 308 (1) ◽  
pp. E40-E50 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo C. Rorato ◽  
Ernane Torres Uchoa ◽  
Paula B. Marangon ◽  
Carol F. Elias ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Body Weight Loss ◽  
Male Rats ◽  
Leptin Resistance ◽  
Reduce Food Intake ◽  
Low Grade ◽  
Lps Treatment

Leptin resistance is induced by the feedback inhibitors tyrosine phosphatase-1B (PTP1B) and decreased Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) signaling. To investigate the participation of PTP1B and SHP-2 in LPS-induced leptin resistance, we injected repeated (6-LPS) intraperitoneal LPS doses (100 μg/kg ip) for comparison with a single (1-LPS) treatment and evaluated the expression of SHP-2, PTP1B, p-ERK1/2, and p-STAT3 in the hypothalamus of male Wistar rats. The single LPS treatment increased the expression of p-STAT3 and PTP1B but not SHP-2. The repeated LPS treatment reduced SHP-2, increased PTP1B, and did not change p-STAT3. We observed that the PTP1B expression induced by the endotoxin was highly colocalized with leptin receptor cells in the hypothalamus of LepRb-IRES-Cre-tdTomato reporter mice. The single, but not the repeated, LPS treatment decreased the food intake and body weight. Leptin had no stimulatory effect on the hypophagia, body weight loss, or pSTAT3 expression in 6-LPS rats, indicating leptin unresponsiveness. Notably, the PTP1B inhibitor (3.0 nmol/rat in 5 μl icv) restored the LPS-induced hypophagia in 6-LPS rats and restored the ability of leptin to reduce food intake and body weight as well as to phosphorylate STAT3 in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus. The present data suggest that an increased PTP1B expression in the hypothalamus underlies the development of leptin resistance during repeated exposure to LPS. Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity.

scholarly journals Short-Term Results Suggest That Sleeved Stomach without Resection Is as Effective as Sleeve Gastrectomy in Improving Glucose Control in Type 2 Diabetes Mellitus Sprague-Dawley Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Wenzhuo Zhang ◽  
Jason Widjaja ◽  
Libin Yao ◽  
Yong Shao ◽  
Xiaocheng Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Sleeve Gastrectomy ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Glucose Control ◽  
Sprague Dawley ◽  
Short Term

Background. Although sleeve gastrectomy results in good weight loss and metabolic improvements, it is an irreversible procedure. Therefore, we attempted to assess the possibility of creating a sleeved stomach without resection. Material and Methods. A total of 22 male Sprague-Dawley rats with type 2 diabetes were randomly assigned into 3 different groups: (1) sleeve gastroplasty with gastric remnant-jejunal anastomosis (SGP, n=8); (2) sleeve gastrectomy (SG, n=8); and (3) SHAM (n=6). Body weight, food intake, fasting blood glucose (FBG), hormonal analysis, and oral glucose tolerance test (OGTT) were performed and measured preoperatively and postoperatively. Results. During the postoperative period, SGP and SG showed significantly lower food intake and body weight when compared with the preoperative levels, respectively (p value < 0.05). Postoperatively, SGP and SG showed improvements in FBG and glucose tolerance levels compared to their respective preoperative levels (p<0.05). FBG and glucose tolerance levels did not differ between SGP and SG postoperatively. SG resulted in a reduction in fasting ghrelin levels when compared with the preoperative level (p<0.05). Fasting insulin levels did not differ preoperatively and postoperatively among all groups. Postoperatively, fasting GLP-1 levels were higher in SGP and SG when compared with the preoperative levels, but no statistical significance was observed. Compared preoperatively, the SGP and SG procedures resulted in a decline in HOMA-IR at postoperative 6th week (p<0.05). Conclusion. Our animal experiment suggested that at least in the short term, sleeved stomach without resection resulted in similar weight loss and improved glucose control effects compared to sleeve gastrectomy.

scholarly journals Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet

2004 ◽  
Vol 183 (2) ◽  
pp. 289-298 ◽  
Author(s):  
G Tulipano ◽  
A V Vergoni ◽  
D Soldi ◽  
E E Muller ◽  
D Cocchi
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Fat Content ◽  
Leptin Resistance ◽  
Calorie Intake ◽  
Sprague Dawley ◽  
High Fat ◽  
Glucose Levels ◽  
Anorectic Effect

Leptin produced by adipocytes controls body weight by restraining food intake and enhancing energy expenditure at the hypothalamic level. The diet-induced increase in fat mass is associated with the presence of elevated circulating leptin levels, suggesting the development of resistance to its anorectic effect. Rats, like humans, show different susceptibility to diet-induced obesity. The aim of the present study was to compare the degree of leptin resistance in obesity-prone (OP) vs obesity-resistant (OR) rats on a moderate high-fat (HF) diet and to establish if the effects of leptin on hypothalamo–pituitary endocrine functions were preserved. Starting from 6 weeks after birth, male Sprague–Dawley rats were fed on either a commercial HF diet (fat content: 20% of total calorie intake) or a standard pellet chow (CONT diet, fat content: 3%). After 12 weeks of diet, rats fed on HF diet were significantly heavier than rats fed on CONT diet. Animals fed on HF diet were ranked according to body weight; the two tails of the distribution were called OP and OR rats respectively. A polyethylene cannula was implanted into the right ventricle of rats 1 week before central leptin administration. After 12 weeks of HF feeding, both OR and OP rats were resistant to central leptin administration (10 μg, i.c.v.) (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 62 [50; 78]; OR, 93 [66; 118]; OP, 90 [70; 120] as medians and 95% confidence intervals (CIs) of six rats for each group). Conversely, after 32 weeks of diet both OR and OP rats were partially responsive to 10 μg leptin i.c.v. as compared with CONT rats (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 60 [50; 67]; OR, 65 [50; 80]; OP, 80 [60; 98] as medians and 95% CIs of six rats for each group); the decrease of food intake following 200 μg leptin i.p. administration was similar in all the three groups (calorie intake as a percent of vehicle-treated rats: 86 [80; 92] as median and 95% CI). The long-term intake of HF diet caused hyperleptinemia, hyperinsulinemia and higher plasma glucose levels in OP rats as compared with CONT rats. Plasma thyroxine (T4) was lower in all the rats fed the HF diet as compared with CONT. i.c.v. administration of leptin after 32 weeks of diet restored normal insulin levels in OP rats. Moreover, leptin increased plasma T4 concentration and strongly enhanced GH mRNA expression in the pituitary of OP as well as OR rats (180±10% vs vehicle-treated rats). In conclusion, long-term intake of HF diet induced a partial central resistance to the anorectic effect of leptin in both lean and fat animals; the neuroendocrine effects of leptin on T4 and GH were preserved.

scholarly journals Role of neonatal hyperleptinaemia on serum adiponectin and suppressor of cytokine signalling-3 expression in young rats

2008 ◽  
Vol 101 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Magna Cottini Fonseca Passos ◽  
Fabiane Pereira Toste ◽  
Sheila Cristina Potente Dutra ◽  
Paula Affonso Trotta ◽  
Fernanda Pereira Toste ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Serum Insulin ◽  
Leptin Resistance ◽  
Serum Adiponectin ◽  
Lower Serum ◽  
Serum Adiponectin Concentration

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 μg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (+42·5 %) and lower levels of serum adiponectin ( − 43·2 %). The hypothalamic expression of OB-Rb was lower ( − 22 %) and SOCS-3 was higher (+52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

scholarly journals Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

2012 ◽  
Vol 302 (1) ◽  
pp. E134-E144 ◽  
Author(s):  
Gregory J. Morton ◽  
Brendan S. Thatcher ◽  
Roger D. Reidelberger ◽  
Kayoko Ogimoto ◽  
Tami Wolden-Hanson ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Area Postrema ◽  
Neuronal Response ◽  
Leptin Resistance ◽  
Low Fat Diet ◽  
Sustained Reduction ◽  
Induce Weight Loss

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky ( fa k/ fa k) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.

scholarly journals Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rat

2006 ◽  
Vol 95 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Fabiane Pereira Toste ◽  
Egberto Gaspar de Moura ◽  
Patrícia Cristina Lisboa ◽  
Aline Teixeira Fagundes ◽  
Elaine de Oliveira ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
The Body ◽  
Leptin Resistance ◽  
Control Group ◽  
Adult Rats ◽  
Leptin Receptors ◽  
Adult Rat ◽  
Anorectic Effect

We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8μg/100g body weight, subcutaneously) for the first 10d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150d old. Food intake was higher in the Lep group (approximately 14%, p<0·05) from day 133 onwards, and body weight was higher (approximately 10%, p<0·05) from day 69 onwards, compared with the control group. At 150d of age, the rats were tested for food intake in response to either leptin (05mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (−40% p<0·05), hyperleptinaemia (+78%, p<0·05), hyperinsulinaemia (+100%, p<0·02), hypertriacylglycerolaemia (+17%, p<0·05) and a higher protein content in the body (+16%, p<0·05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.

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.

Protein appetite is increased after central leptin-induced fat depletion

2007 ◽  
Vol 293 (4) ◽  
pp. R1468-R1473 ◽  
Author(s):  
Michael F. Wiater ◽  
Bryan D. Hudson ◽  
Yvette Virgin ◽  
Sue Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Caloric Intake ◽  
Sprague Dawley ◽  
Body Protein ◽  
Macronutrient Selection ◽  
Daily Diet ◽  
Nadir Point ◽  
And Control

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a “fatless” animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.

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