scholarly journals Effects of Acute Changes in Neonatal Leptin Levels on Food Intake and Long-Term Metabolic Profiles in Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4116-4126 ◽  
Author(s):  
Miriam Granado ◽  
Cristina García-Cáceres ◽  
Esther Fuente-Martín ◽  
Francisca Díaz ◽  
Virginia Mela ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Metabolic Effects ◽  
Metabolic Profiles ◽  
Mrna Levels ◽  
Reduced Body ◽  
Acute Changes

In rodents there is a rise in serum leptin levels between postnatal days (PND) 5 and 14, with this neonatal leptin surge reported to modulate the maturation of hypothalamic circuits involved in appetite regulation. We hypothesized that acute changes in neonatal leptin levels have different long-term metabolic effects depending on how and when this surge is modified. To advance the timing of the normal leptin peak, male Wistar rats were injected with leptin (sc, 3 μg/g) on PND 2. To ablate the leptin peak on PND 10, a pegylated leptin antagonist (sc, 9 μg/g) was injected. Controls received vehicle. All rats were allowed to eat ad libitum until PND 150. Increased leptin on PND 2 reduced food intake (P < 0.01) after 3 months of age with no effect on body weight. Levels of total ghrelin were reduced (P < 0.001) and acylated ghrelin increased (P < 0.05), with no other modifications in metabolic hormones. In contrast, treatment with the leptin antagonist on PND 9 did not affect food intake but reduced body weight beginning around PND 60 (P < 0.02). This was associated with a reduction in fat mass, insulin (P < 0.01), and leptin (P < 0.007) levels and an increase in testosterone levels (P < 0.01). Hypothalamic neuropeptide Y (P < 0.05) and leptin receptor (P < 0.005) mRNA levels were reduced, whereas mRNA levels for uncoupling protein 2 (P < 0.005) were increased in visceral fat, which may indicate an increase in energy expenditure. In conclusion, acute changes in neonatal leptin levels induce different metabolic profiles depending on how and when leptin levels are modified.

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). Whereas PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P < 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P < 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P < 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

2006 ◽  
Vol 291 (2) ◽  
pp. R367-R375 ◽  
Author(s):  
Niels Vrang ◽  
Andreas Nygaard Madsen ◽  
Mads Tang-Christensen ◽  
Gitte Hansen ◽  
Philip Just Larsen
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Peptide Yy ◽  
Body Weight Gain ◽  
Subcutaneous Administration ◽  
Treated Group ◽  
Metabolic Effects ◽  
Male Rats ◽  
Reduced Body ◽  
Gut Hormone

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3–36) in mice and rats, as well as metabolic effects of chronic PYY(3–36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3–36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 μg·kg−1·day−1) of PYY(3–36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 μg·kg−1·day−1) of PYY(3–36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 μg·kg−1·day−1 PYY(3–36) weighed ∼10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3–36) (250 and 1,000 μg·kg−1·day−1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 μg/kg PYY(3–36) elicited a conditioned taste aversion in male rats.

scholarly journals Long-term CCK-leptin synergy suggests a role for CCK in the regulation of body weight

1999 ◽  
Vol 276 (4) ◽  
pp. R1038-R1045 ◽  
Author(s):  
Claire A. Matson ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Intraperitoneal Injection ◽  
Sucrose Intake ◽  
Reduced Body ◽  
Single Intraperitoneal Injection

The gut peptide CCK is a nutrient-related signal important to the control of food intake. In the present studies, we observed that a single intraperitoneal injection of CCK (1–2 μg/kg) given 2–3 h after intracerebroventricular leptin (2–5 μg) reduced body weight and chow intake over the ensuing 48 h more than did leptin alone. CCK alone had no effect on either 48-h chow intake or body weight but significantly reduced feeding during a 30-min sucrose test. However, reduction of 30-min sucrose intake by CCK was not enhanced by prior intracerebroventricular leptin. The present data suggest that CCK can contribute to the regulation of body weight when central leptin levels are elevated.

scholarly journals Food Intake and Core Body Temperature of Pups and Adults in a db Mouse Line Deficient in the Long Form of the Leptin Receptor without Misty Mutation

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wijang Pralampita Pulong ◽  
Miharu Ushikai ◽  
Emi Arimura ◽  
Masaharu Abe ◽  
Hiroaki Kawaguchi ◽  
...  
Keyword(s):  
Food Intake ◽  
Body Temperature ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Core Body Temperature ◽  
Mrna Levels ◽  
Mouse Line ◽  
Brown Adipose ◽  
Long Form ◽  
Core Body

Different involvement of leptin signaling in food intake (FI) and body temperature (BT) in pups and adults has been suggested. However, the leptin receptor (Lepr) long-form-deficient (db) mouse line has not been fully examined in pups. In the most available db mouse line, wild-type (WT) mice have a mutation in the dedicator of cytokinesis 7 gene, named misty, which was recently revealed to be involved in neuronal development. Therefore, we established a line of db mice without the misty mutation using natural mating. Adult (8 weeks of age) homozygous db/db mice displayed significantly higher core body weight (BW) and FI and significantly lower core BT than WT mice. However, postnatal (2 weeks of age) db/db mice displayed similar BW and milk intake and significantly lower core BT than WT mice. Correspondingly, adult and postnatal db/db mice exhibited altered mRNA levels of hypothalamic orexigenic and anorexigenic peptide in adults but not in pups. Additionally, db/db mice displayed significantly lower mRNA levels of brown adipose tissue uncoupling protein 1 at both ages. In conclusion, the db mouse line without the misty mutation clearly showed the different involvements of the Lepr long form in FI and BT in pups and adults.

Mechanisms of Amylin/Leptin Synergy in Rodent Models

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Victoria F. Turek ◽  
James L. Trevaskis ◽  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell ◽  
Boman Irani ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Therapeutic Potential ◽  
Ventromedial Hypothalamus ◽  
Signal Transducer ◽  
Leptin Signaling ◽  
Reduced Body ◽  
Epididymal Fat ◽  
Transcription 3

Abstract The present studies aimed to identify mechanisms contributing to amylin/leptin synergy in reducing body weight and adiposity. We reasoned that if amylin/leptin harnessed complementary neuronal pathways, then in the leptin-sensitive state, amylin should augment leptin signaling/binding and that in the absence of endogenous amylin, leptin signaling should be diminished. Amylin (50 μg/kg, ip) amplified low-dose leptin-stimulated (15 μg/kg, ip) phosphorylated signal transducer and activator of transcription-3 signaling within the arcuate nucleus (ARC) in lean rats. Amylin (50 μg/kg · d) or leptin (125 μg/kg · d) infusion to lean rats decreased 28-d food intake (14 and 10%, respectively), body weight (amylin by 4.3%, leptin by 4.9%), and epididymal fat (amylin by 19%, leptin by 37%). Amylin/leptin co-infusion additively decreased food intake (by 26%) and reduced body weight (by 15%) and epididymal fat (by 78%; all P < 0.05 vs. all groups) in a greater than mathematically additive manner, consistent with synergy. Amylin increased leptin binding within the ventromedial hypothalamus (VMN) by 35% and dorsomedial hypothalamus by 47% (both P < 0.05 vs. vehicle). Amylin/leptin similarly increased leptin binding in the VMN by 40% and ARC by 70% (P < 0.05 vs. vehicle). In amylin-deficient mice, hypothalamic leptin receptor mRNA expression was reduced by 50%, leptin-stimulated phosphorylated signal transducer and activator of transcription-3 within ARC and VMN was reduced by 40%, and responsiveness to leptin’s (1 mg/kg · d for 28 d) weight-reducing effects was attenuated (all P < 0.05 vs. wild-type controls). We suggest that amylin/leptin’s marked weight- and fat-reducing effects are due to activation of intrinsic synergistic neuronal signaling pathways and further point to the integrated neurohormonal therapeutic potential of amylin/leptin agonism in obesity.

Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin

2005 ◽  
Vol 289 (1) ◽  
pp. E40-E45 ◽  
Author(s):  
Denis Arsenijevic ◽  
Eva Gallmann ◽  
William Moses ◽  
Thomas Lutz ◽  
Charlotte Erlanson-Albertsson ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Food Intake ◽  
Food Access ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Postprandial Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Epididymal Fat

This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARα, -β, -γ1, and -γ2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARγ2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure.

scholarly journals Chronic Hindbrain Administration of Oxytocin Elicits Weight Loss in Male Diet-Induced Obese Mice

2021 ◽  
Author(s):  
Melise Marie Edwards ◽  
Ha Khanh Nguyen ◽  
Adam Jay Herbertson ◽  
Andrew Dale Dodson ◽  
Tomasz Wietecha ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Intake ◽  
Uncoupling Protein ◽  
Post Injection ◽  
Reduced Body ◽  
Brown Adipose ◽  
Pre Treatment

Previous studies indicate that oxytocin (OT) administration reduces body weight in high fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake and body composition. OT reduced body weight by approximately 4.5±1.4% in DIO mice relative to OT pre-treatment body weight (P<0.05). These effects were associated with reduced adiposity and adipocyte size (inguinal white adipose tissue (IWAT)] (P<0.05) and attributed, in part, to reduced energy intake (P<0.05) at a dose that did not increase kaolin intake (P=NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05<P<0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (TIBAT). 4V OT (1 μg) elevated TIBAT at 0.75 (P=0.08), 1, and 1.25 h (P<0.05) post-injection; a higher dose (5 μg) elevated TIBAT at 0.75, 1, 1.25, 1.5, 1.75 (P<0.05), and 2-h (0.05<P<0.1) post-injection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.

Long-term metabolic benefits of exenatide in mice are mediated solely via the known glucagon-like peptide 1 receptor

2014 ◽  
Vol 306 (7) ◽  
pp. R490-R498 ◽  
Author(s):  
Krystyna Tatarkiewicz ◽  
Emmanuel J. Sablan ◽  
Clara J. Polizzi ◽  
Christiane Villescaz ◽  
David G. Parkes
Keyword(s):  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 receptors (GLP-1R) are expressed in multiple tissues and activation results in metabolic benefits including enhanced insulin secretion, slowed gastric emptying, suppressed food intake, and improved hepatic steatosis. Limited and inconclusive knowledge exists regarding whether the effects of chronic exposure to a GLP-1R agonist are solely mediated via this receptor. Therefore, we examined 3-mo dosing of exenatide in mice lacking a functional GLP-1R (Glp1r−/−). Exenatide (30 nmol·kg−1·day−1) was infused subcutaneously for 12 wk in Glp1r−/− and wild-type (Glp1r+/+) control mice fed a high-fat diet. Glycated hemoglobin A1c (HbA1c), plasma glucose, insulin, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight, food intake, terminal hepatic lipid content (HLC), and plasma exenatide levels were measured. At the end of the study, oral glucose tolerance test (OGTT) and rate of gastric emptying were assessed. Exenatide produced no significant changes in Glp1r−/− mice at study end. In contrast, exenatide decreased body weight, food intake, and glucose in Glp1r+/+ mice. When compared with vehicle, exenatide reduced insulin, OGTT glucose AUC0–2h, ALT, and HLC in Glp1r+/+ mice. Exenatide had no effect on plasma amylase or lipase levels. Exenatide concentrations were approximately eightfold higher in Glp1r−/− versus Glp1r+/+ mice after 12 wk of infusion, whereas renal function was similar. These data support the concept that exenatide requires a functional GLP-1R to exert chronic metabolic effects in mice, and that novel “GLP-1” receptors may not substantially contribute to these changes. Differential exenatide plasma levels in Glp1r+/+ versus Glp1r−/− mice suggest that GLP-1R may play an important role in plasma clearance of exenatide and potentially other GLP-1-related peptides.

scholarly journals Impact of obesity and leptin treatment on adipocyte gene expression in Psammomys obesus

2000 ◽  
Vol 164 (1) ◽  
pp. 45-50 ◽  
Author(s):  
A Sanigorski ◽  
D Cameron-Smith ◽  
P Lewandowski ◽  
K Walder ◽  
A de Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Food Intake ◽  
Fat Mass ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Leptin Resistance ◽  
Mrna Levels ◽  
Psammomys Obesus ◽  
Glycerol Phosphate

We examined the effects of leptin treatment on the expression of key genes in adipocyte metabolism in Psammomys obesus (P. obesus), a polygenic rodent model of obesity. Lean and obese P. obesus were given three daily intraperitoneal injections of either saline or leptin (total of 45 mg/kg per day) for 7 days. In lean animals, leptin treatment led to reductions in food intake, body weight and fat mass. Pair-fed animals matched for the reduction in food intake of the lean leptin-treated animals demonstrated similar reductions in body weight and fat mass. In obese P. obesus, leptin treatment failed to have any effect on body weight or body fat mass, indicating leptin resistance. Lipoprotein lipase, hormone-sensitive lipase and peroxisome proliferator activated receptor gamma 2 mRNA levels were significantly reduced in lean leptin-treated animals, whereas pair-fed animals were similar to lean controls. Uncoupling protein 2 and glycerol phosphate acyltransferase were also reduced in the lean leptin-treated animals, but not significantly so. Obese animals did not show any gene expression changes after leptin treatment. In conclusion, high circulating concentrations of leptin in lean P. obesus resulted in decreased gene expression of a number of key lipid enzymes, independent of changes in food intake, body weight and fat mass. These effects of leptin were not found in obese P. obesus.

scholarly journals Deficiency of PTP1B in Leptin Receptor-Expressing Neurons Leads to Decreased Body Weight and Adiposity in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4227-4237 ◽  
Author(s):  
Ryan C. Tsou ◽  
Derek J. Zimmer ◽  
Bart C. De Jonghe ◽  
Kendra K. Bence
Keyword(s):  
Body Weight ◽  
Leptin Receptor ◽  
Body Weight Gain ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Leptin Signaling ◽  
Reduced Body ◽  
Leptin Sensitivity

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed tyrosine phosphatase implicated in the negative regulation of leptin and insulin receptor signaling. PTP1B−/− mice possess a lean metabolic phenotype attributed at least partially to improved hypothalamic leptin sensitivity. Interestingly, mice lacking both leptin and PTP1B (ob/ob:PTP1B−/−) have reduced body weight compared with mice lacking leptin only, suggesting that PTP1B may have important leptin-independent metabolic effects. We generated mice with PTP1B deficiency specifically in leptin receptor (LepRb)-expressing neurons (LepRb-PTP1B−/−) and compared them with LepRb-Cre-only wild-type (WT) controls and global PTP1B−/− mice. Consistent with PTP1B's role as a negative regulator of leptin signaling, our results show that LepRb-PTP1B−/− mice are leptin hypersensitive and have significantly reduced body weight when maintained on chow or high-fat diet (HFD) compared with WT controls. LepRb-PTP1B−/− mice have a significant decrease in adiposity on HFD compared with controls. Notably, the extent of attenuated body weight gain on HFD, as well as the extent of leptin hypersensitivity, is similar between LepRb-PTP1B−/− mice and global PTP1B−/− mice. Overall, these results demonstrate that PTP1B deficiency in LepRb-expressing neurons results in reduced body weight and adiposity compared with WT controls and likely underlies the improved metabolic phenotype of global and brain-specific PTP1B-deficient models. Subtle phenotypic differences between LepRb-PTP1B−/− and global PTP1B−/− mice, however, suggest that PTP1B independent of leptin signaling may also contribute to energy balance in mice.

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