scholarly journals Robust Reductions of Body Weight and Food Intake by an Oxytocin Analog in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Clinton T. Elfers ◽  
James E. Blevins ◽  
Elizabeth A. Lawson ◽  
Richard Pittner ◽  
David Silva ◽  
...  
Keyword(s):  
Body Weight ◽  
Locomotor Activity ◽  
Food Intake ◽  
Dose Escalation ◽  
Male Rats ◽  
Reduce Food Intake ◽  
Vehicle Treatment ◽  
Drug Interventions ◽  
Oxytocin Analog

Background: Oxytocin is a hypothalamic neuropeptide that participates in the network of appetite regulation. Recently the oxytocin signaling pathway has emerged as an attractive target for treating obesity. However, the short half-life limits its development as a clinical therapeutic. Here we provide results from testing a long-lasting, potent and selective oxytocin analog ASK1476 on its efficacy to reduce food intake and body weight in comparison to the native oxytocin peptide.Methods: ASK1476 features two specific amino acid substitutions in positions 7 and 8 combined with a short polyethylene glycol spacer. Short time dose escalation experiments testing increasing doses of 3 days each were performed in diet-induced overweight (DIO) male rats assessing effects on body weight as well as changes in food intake. Furthermore, DIO rats were tested for changes in body weight, food intake, temperature, and locomotor activity over 28 days of treatment (oxytocin, ASK1476, or vehicle).Results: In dose escalation experiments, significant reductions in food intake relative to baseline were detected beginning with doses of 15 nmol/kg ASK1476 (−15.2 ± 2.3 kcal/d, p = 0.0017) and 20 nmol/kg oxytocin (−11.2.9 ± 2.4 kcal/d, p = 0.0106) with corresponding significant changes in body weight (ASK1476: −5.2 ± 0.8 g, p = 0.0016; oxytocin: −2.6 ± 0.7 g, p = 0.0326). In long-term experiments, there was no difference on body weight change between 120 nmol/kg/d ASK1476 (−71.4 ± 34.2 g, p = 0.039) and 600 nmol/kg/d oxytocin (−91.8 ± 32.2 g, p = 0.035) relative to vehicle (706.9 ± 28.3 g), indicating a stronger dose response for ASK1476. Likewise, both ASK1476 and oxytocin at these doses resulted in similar reductions in 28-day cumulative food intake (ASK1476: −562.7 ± 115.0 kcal, p = 0.0001; oxytocin: −557.1 ± 101.3 kcal, p = 0.0001) relative to vehicle treatment (2716 ± 75.4 kcal), while no effects were detected on locomotor activity or body temperature.Conclusion: This study provides proof-of-concept data demonstrating an oxytocin analog with extended in vivo stability and improved potency to reduce food intake and body weight in DIO animals which could mark a new avenue in anti-obesity drug interventions.

scholarly journals CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Molecular Forms ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Sprague Dawley ◽  
Solid Meal ◽  
Sprague Dawley Rats ◽  
And Behavior

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.

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 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 Dietary whey reduces energy intake and alters hypothalamic gene expression in obese phyto-oestrogen-deprived male rats

2016 ◽  
Vol 116 (6) ◽  
pp. 1125-1133 ◽  
Author(s):  
María F. Andreoli ◽  
Cora Stoker ◽  
Gisela P. Lazzarino ◽  
Guillermina Canesini ◽  
Enrique H. Luque ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Intake ◽  
Thyroid Stimulating Hormone ◽  
Male Rats ◽  
Reduce Food Intake ◽  
Hormonal Changes ◽  
Glucose Homoeostasis ◽  
Obesity And Diabetes ◽  
Oestrogen Deprivation

AbstractRemoving dietary phyto-oestrogens in adult male rats causes obesity and diabetes. As whey proteins have been reported to reduce food intake and improve glucose homoeostasis, we investigated whether they could attenuate susceptibility to obesity and diabetes due to phyto-oestrogen deprivation. To this end, thirty male Wistar rats were fed a high-phyto-oestrogen (HP) or a phyto-oestrogen-free (PF) diet for 10 weeks; six rats from each group were killed. The remaining HP animals (six animals) continued receiving the HP diet for 6 weeks. The remaining PF rats (twelve rats) were divided in two groups: one was given the PF diet and the other a variation of the PF diet plus whey protein (PF-W). Body weight, food intake and adipose tissue weights were recorded. Hypothalamic mRNA expressions of orexigenic (neuropeptide Y, agouti-related protein (AgRP)) and anorexigenic (pro-opiomelanocortin (POMC), cocaine-amphetamine-related transcript (CART)) neuropeptides were quantified by real-time PCR. Serum glucose, insulin and total thyroxine (T4), thyroid-stimulating hormone, testosterone and oestradiol were assessed. After 10 weeks of PF diet, increased body weight, adiposity and energy intake, with up-regulation of AgRP and down-regulation of POMC', were observed. Longer treatment exacerbated these results, increased total T4 levels, reduced oestradiol levels and impaired glucose homoeostasis. PF-W reduced energy intake and increased POMC expression; however, body weight and adiposity remained unchanged. PF-W could not prevent the hormonal changes or the high circulating glucose levels induced by phyto-oestrogen deprivation, but reduced fasting insulin. These data demonstrate that, although 6 weeks of whey administration could not prevent obesity in phyto-oestrogen-deprived rats, the reduction in energy intake and circulating insulin could be beneficial with longer treatments.

Effect of combination of peripheral oxytocin and naltrexone at subthreshold doses on food intake, body weight and feeding-related brain gene expression in male rats

2021 ◽  
pp. 113464
Author(s):  
Mitchell A. Head ◽  
Allen S. Levine ◽  
David G. Christian ◽  
Anica Klockars ◽  
Pawel K. Olszewski
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Food Intake ◽  
Male Rats ◽  
Brain Gene Expression

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

The effects of chronic nicotine on meal patterns, food intake, metabolism and body weight of male rats

2010 ◽  
Vol 95 (1) ◽  
pp. 92-99 ◽  
Author(s):  
L.L. Bellinger ◽  
P.J. Wellman ◽  
R.B.S. Harris ◽  
E.W. Kelso ◽  
P.R. Kramer
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Male Rats ◽  
Meal Patterns ◽  
Chronic Nicotine

scholarly journals In vitro and in vivo Activities of Psidium guajava and Azadirachta indica Leaf Extracts and solvent Fractions against Salmonella Typhi

2021 ◽  
pp. 56-71
Author(s):  
Adetutu Adewale ◽  
Olaniyi Deborah Temitope ◽  
Awodugba Tamilore ◽  
Owoade Abiodun Olusoji ◽  
Olaniyan, Lamidi Waheed B. ◽  
...  
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Sub Saharan Africa ◽  
Male Rats ◽  
Carrier Status ◽  
Leaf Extracts ◽  
Salmonella Infections ◽  
Neem Leaves

Typhoidal salmonella infections remain a challenge in the health care system in sub-Saharan Africa. Carrier status and advent of multi-drug resistant S. Typhi strains have necessitated the search for new drug leads. Hence, this study aims at investigating P. guajava and A. indica leaves for anti-salmonella activities. Guava and neem leaves were extracted by maceration in methanol and fractionated by solvent partitioning. In vitro activities were assessed by agar well diffusion and broth micro-dilution methods. Sixty male rats were randomized to 10 groups of 6 animals each for the in vivo experiments. Groups of rats except, normal control, were induced with 0.5McFarland of S. Typhi suspension orally. Treatment groups received 200 mg/kg body weight of extracts and fractions, and the control groups were treated with 14.29mg/kg body weight of ciprofloxacin and 1%v/v DMSO for 7 days post-infection. Biochemical parameters were determined spectrophotometrically. Hematological parameters were analyzed with automated hematology diagnostic machine. All fractions of P. guajava and three of A. indica inhibited S. Typhi growth with Zone of Inhibition (ZI) ranging from 11-15 mm. Active fractions inhibited 48.60-62.45% of S. Typhi biofilm formation at 25 mg/mL with Minimum Bactericidal Inhibitory Concentration (MBIC) of 0.39-12.5 mg/mL. All fractions improved body weight of treated rats and inhibited bacteremia at 44.75 and 95.94%. Hematological parameters improved in all fractions-treated rats. MDA was not significantly (p<0.05) altered in all groups. One fraction of P. guajava (ePg) lowered the elevated level in concentration of Nitric oxide (NO) while all fractions enhanced the lowered activity of SOD. Elevated (lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (BIL) were lowered by all fractions to various extents in treated rats. Fractions of P. guajava, and A. indica could be further considered for identification of active anti-salmonella principle(s).

scholarly journals In VivoEffects of Leptin-Related Synthetic Peptides on Body Weight and Food Intake in Female ob/obMice: Localization of Leptin Activity to Domains Between Amino Acid Residues 106–140*

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1413-1418 ◽  
Author(s):  
Patricia Grasso ◽  
Matthew C. Leinung ◽  
Stacy P. Ingher ◽  
Daniel W. Lee
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Amino Acid ◽  
Food Intake ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Amino Acid Residues ◽  
Inactive Form ◽  
In Vivo Effects

Abstract In C57BL/6J ob/ob mice, a single base mutation of the ob gene in codon 105 results in the replacement of arginine by a premature stop codon and production of a truncated inactive form of leptin. These observations suggest that leptin activity may be localized, at least in part, to domains distal to amino acid residue 104. To investigate this possibility, we synthesized six overlapping peptide amides corresponding to residues 106–167 of leptin, and examined their effects on body weight and food intake in female C57BL/6J ob/ob mice. When compared with vehicle-injected control mice, weight gain by mice receiving 28 daily 1-mg ip injections of LEP-(106–120), LEP-(116–130), or LEP-(126–140) was significantly (P &lt; 0.01) reduced with no apparent toxicity. Weight gain by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167) was not significantly different from that of vehicle-injected control mice. The effects of LEP-(106–120), LEP-(116–130), or LEP-(126–140) were most pronounced during the first week of peptide treatment. Within 7 days, mice receiving these peptides lost 12.3%, 13.8%, and 9.8%, respectively, of their initial body weights. After 28 days, mice given vehicle alone, LEP-(136–150), LEP-(146–160), or LEP-(156–167) were 14.7%, 20.3%, 25.0%, and 24.8% heavier, respectively, than they were at the beginning of the study. Mice given LEP-(106–120) or LEP-(126–140) were only 1.8% and 4.2% heavier, respectively, whereas mice given LEP-(116–130) were 3.4% lighter. Food intake by mice receiving LEP-(106–120), LEP-(116–130), or LEP-(126–140), but not by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167), was reduced by 15%. The results of this study indicate 1) that leptin activity is localized, at least in part, in domains between residues 106–140; 2) that leptin-related peptides have in vivo effects similar to those of native leptin; and 3) offer hope for development of peptide analogs of leptin having potential application in human or veterinary medicine.

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