Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity

2002 ◽  
Vol 8 (2) ◽  
pp. 179-183 ◽  
Author(s):  
Ellen L. Air ◽  
Mathias Z. Strowski ◽  
Stephen C. Benoit ◽  
Stacey L. Conarello ◽  
Gino M. Salituro ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Small Molecule ◽  
Reduce Food Intake

Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice

2006 ◽  
Vol 89 (5) ◽  
pp. 687-691 ◽  
Author(s):  
Lynda M. Brown ◽  
Deborah J. Clegg ◽  
Stephen C. Benoit ◽  
Stephen C. Woods
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Reduce Food Intake

scholarly journals Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1–28 to Pomc−/− mice reduces food intake and weight but does not affect adrenal growth or corticosterone production

2006 ◽  
Vol 190 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Anthony P Coll ◽  
Martin Fassnacht ◽  
Steffen Klammer ◽  
Stephanie Hahner ◽  
Dominik M Schulte ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Reduce Food Intake ◽  
Appetite Control ◽  
Concurrent Administration ◽  
Physiological Level ◽  
Sham Treatment ◽  
Acth Treatment

Pro-opiomelanocortin (POMC) is a polypeptide precursor that undergoes extensive processing to yield a range of peptides with biologically diverse functions. POMC-derived ACTH is vital for normal adrenal function and the melanocortin α-MSH plays a key role in appetite control and energy homeostasis. However, the roles of peptide fragments derived from the highly conserved N-terminal region of POMC are less well characterized. We have used mice with a null mutation in the Pomc gene (Pomc−/−) to determine the in vivo effects of synthetic N-terminal 1–28 POMC, which has been shown previously to possess adrenal mitogenic activity. 1–28 POMC (20 μg) given s.c. for 10 days had no effect on the adrenal cortex of Pomc−/− mice, with resultant cortical morphology and plasma corticosterone levels being indistinguishable from sham treatment. Concurrent administration of 1–28 POMC and 1–24 ACTH (30 μg/day) resulted in changes identical to 1–24 ACTH treatment alone, which consisted of upregulation of steroidogenic enzymes, elevation of corticosterone levels, hypertrophy of the zona fasciculate, and regression of the X-zone. However, treatment of corticosterone-depleted Pomc−/− mice with 1–28 POMC reduced cumulative food intake and total body weight. These anorexigenic effects were ameliorated when the peptide was administered to Pomc−/− mice with circulating corticosterone restored either to a low physiological level by corticosterone-supplemented drinking water (CORT) or to a supraphysiological level by concurrent 1–24 ACTH administration. Further, i.c.v. administration of 1–28 POMC to CORT-treated Pomc−/− mice had no effect on food intake or body weight. In wild-type mice, the effects of 1–28 POMC upon food intake and body weight were identical to sham treatment, but 1–28 POMC was able to ameliorate the hyperphagia induced by concurrent 1–24 ACTH treatment. In a mouse model which lacks all endogenous POMC peptides, s.c. treatment with synthetic 1–28 POMC alone can reduce food intake and body weight, but has no impact upon adrenal growth or steroidogenesis.

scholarly journals Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7–36) Amide or Exendin-(9–39) Alters Body Weight in the Rat**This work was supported by the United Kingdom Medical Research Council.

Endocrinology ◽  
1999 ◽  
Vol 140 (1) ◽  
pp. 244-250 ◽  
Author(s):  
Karim Meeran ◽  
Donal O’Shea ◽  
C. Mark B. Edwards ◽  
Mandy D. Turton ◽  
Melanie M. Heath ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Research Council ◽  
Medical Research Council ◽  
Reduce Food Intake ◽  
The United Kingdom ◽  
Ad Libitum ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Central nervous system glucagon-like peptide-1-(7–36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (icv) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9–39), affects food intake and body weight. Daily icv injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 ± 5 g (P < 0.02 compared with saline-injected controls). Daily icv administration of 30 nmol exendin-(9–39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 ± 2 g (P < 0.02 compared with saline-injected controls). Twice daily icv injections of 30 nmol exendin-(9–39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 ± 4 g compared with 14 ± 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to icv GLP-1 or exendin-(9–39). GLP-1 may thus be involved in the regulation of body weight in the rat.

scholarly journals PRL-Releasing Peptide Interacts with Leptin to Reduce Food Intake and Body Weight

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 368-374 ◽  
Author(s):  
Kate L. J. Ellacott ◽  
Catherine B. Lawrence ◽  
Nancy J. Rothwell ◽  
Simon M. Luckman
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Reduce Food Intake

scholarly journals Effects of estradiol and progesterone on food intake, body weight, and carcass adiposity in weanling rats

1981 ◽  
Vol 240 (5) ◽  
pp. E499-E503 ◽  
Author(s):  
S. M. Schwartz ◽  
G. N. Wade
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Reduce Food Intake ◽  
Reduced Body ◽  
Adipose Tissue Lipoprotein Lipase

The effects of estradiol and progesterone on food intake, body weight, carcass adiposity, and adipose tissue lipoprotein lipase (LPL) activity were investigated in weanling female rats. Treatment with estradiol benzoate (EB) reduced body weight gain in ovariectomized (OVX) weanlings as it does in adults. However, other responses to EB were attenuated or absent in weanlings. EB treatment did not reduce food intake, carcass adiposity, or adipose tissue LPL activity. This impaired responsiveness to EB may be due to decreased levels of cytoplasmic estrogen receptors in liver and adipose tissue (but not hypothalamus) in weanlings. On the other hand, responsiveness to progesterone was adultlike in weanlings. Treatment of OVX, EB-primed weanlings with progesterone increased food intake, body weight gain, and carcass adiposity. This adultlike responsiveness to progesterone was associated with adultlike levels of adipose tissue progestin receptors. However, progesterone treatment did not increase adipose tissue LPL activity in weanlings, indicating that changes in LPL activity are not necessary for progesterone-induced obesity.

scholarly journals Long Term Exendin-4 Treatment Reduces Food Intake and Body Weight and Alters Expression of Brain Homeostatic and Reward Markers

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3473-3483 ◽  
Author(s):  
Yan Yang ◽  
Alexander A. Moghadam ◽  
Zachary A. Cordner ◽  
Nu-Chu Liang ◽  
Timothy H. Moran
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Food Intake ◽  
Repeated Administration ◽  
Reduce Food Intake ◽  
Related Protein ◽  
Sprague Dawley ◽  
Long Acting ◽  
Rebound Increase ◽  
Agouti Gene

Abstract Repeated administration of the long-acting glucagon-like peptide 1 receptor agonist exendin-4 (EX-4) has been shown to reduce food intake and body weight and do so without a rebound increase in food intake after treatment termination. The current study examines the neural mechanisms underlying these actions. After 6 weeks of maintenance on a standard chow or a high-fat (HF) diet, male Sprague Dawley rats were treated with EX-4 (3.2 μg/kg, ip, twice a day) or vehicle for 9 consecutive days. Food intake and body weight (BW) were monitored daily. Expression of the genes for the hypothalamic arcuate nucleus (ARC) peptides proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti gene-related protein was determined. Expression of the dopamine precursor tyrosine hydroxylase (TH) gene in the ventral tegmental area and genes for dopamine receptors 1 (D1R) and dopamine receptor 2 in the nucleus accumbens were also determined. Pair-fed groups were included to control for the effects of reduced food intake and BW. Treatment with EX-4 significantly decreased food intake and BW over the 9-day period in both the standard chow and HF groups. HF feeding decreased POMC without changing NPY/agouti gene-related protein gene expression in the ARC. Treatment with EX-4 increased POMC and decreased NPY expression independent of the reduction of food intake and BW. Mesolimbic TH and D1R gene expression were decreased significantly in chronic HF diet-fed rats, and these changes were reversed in both EX-4 and pair-fed conditions. These results suggest a role for increased POMC and decreased NPY expression in the ARC in the effects of EX-4 on food intake and BW. Our findings also suggest that EX-4 induced the recovery of mesolimbic TH and D1R expression in HF diet-fed rats may be secondary to HF intake reduction and/or weight loss.

scholarly journals Multiple cycles of repeated treatments with a Phaseolus vulgaris dry extract reduce food intake and body weight in obese rats

2011 ◽  
Vol 106 (5) ◽  
pp. 762-768 ◽  
Author(s):  
Mauro A. M. Carai ◽  
Noemi Fantini ◽  
Barbara Loi ◽  
Giancarlo Colombo ◽  
Gian Luigi Gessa ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Phaseolus Vulgaris ◽  
Treatment Phase ◽  
Reduce Food Intake ◽  
Dry Extract ◽  
Daily Food Intake ◽  
Daily Food ◽  
Multiple Cycles ◽  
Dose Dependent

Previous lines of experimental evidence have suggested that Phaseolus vulgaris extracts reduce food intake, body weight, lipid accumulation, hedonic properties of food, carbohydrate absorption and metabolism, and glycaemia in rats. The present study was designed to assess the effect of multiple cycles of repeated treatments with a standardised P. vulgaris dry extract on daily food intake and body weight in genetically obese Zucker fa/fa rats (Expt 1). Additionally, the study tested the effect of acute treatment with P. vulgaris dry extract on postprandial glycaemia in Zucker fa/fa rats (Expt 2). In Expt 1, P. vulgaris dry extract was administered daily, at doses of 50 and 500 mg/kg, in three 5 d treatment periods followed by three 20 d off-treatment periods. Administration of P. vulgaris dry extract resulted in dose-dependent decreases in daily food intake and body weight in each treatment phase. Reductions in food intake were of comparable magnitude in each treatment phase. In Expt 2, food-deprived rats were acutely treated with 50 and 500 mg P. vulgaris dry extract per kg immediately before access to a fixed amount of a starch-enriched chow. Treatment with P. vulgaris dry extract resulted in a dose-dependent suppression of glycaemia. These results extend previous data on the anorectic and hypoglycaemic effects of the P. vulgaris dry extract to a validated animal model of obesity. Together with data published previously in the literature, these results strengthen the hypothesis that potentially effective, novel pharmacotherapies for obesity and related disorders may originate from extracts and derivatives of P. vulgaris.

scholarly journals Insulin and Leptin Combine Additively to Reduce Food Intake and Body Weight in Rats

Endocrinology ◽  
2002 ◽  
Vol 143 (6) ◽  
pp. 2449-2452 ◽  
Author(s):  
Ellen L. Air ◽  
Stephen C. Benoit ◽  
Deborah J. Clegg ◽  
Randy J. Seeley ◽  
Stephen C. Woods
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Reduce Food Intake
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