Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers

2007 ◽  
Vol 292 (5) ◽  
pp. R1810-R1818 ◽  
Author(s):  
Claire J. Stocker ◽  
Ed Wargent ◽  
Jacqueline O'Dowd ◽  
Claire Cornick ◽  
John R. Speakman ◽  
...  
Keyword(s):  
Weight Gain ◽  
Energy Balance ◽  
Glucose Tolerance ◽  
Female Offspring ◽  
Male Offspring ◽  
Male Rats ◽  
Fat Pad ◽  
Plasma Insulin Concentration ◽  
Obesogenic Diet ◽  
Tolerance Curve

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg·kg−1·day−1) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.

scholarly journals The effect of moderate consumption of non-nutritive sweeteners on glucose tolerance and body composition in rats

2017 ◽  
Vol 42 (11) ◽  
pp. 1225-1227 ◽  
Author(s):  
Ashley P. Tovar ◽  
James W. Navalta ◽  
Laura J. Kruskall ◽  
John C. Young
Keyword(s):  
Body Composition ◽  
Drinking Water ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Fat Distribution ◽  
Male Rats ◽  
Percent Body Fat ◽  
Fat Pad ◽  
Total Fat

Glucose tolerance and body composition were determined in male rats given non-nutritive sweeteners (NNS) (aspartame or sucralose) in drinking water. Areas under the curve for glucose and insulin with NNS did not differ from control. NNS treatment had no effect on weight gain or percent body fat. Epididymal fat pad mass was higher with aspartame and the ratio of trunk to total fat was less with sucralose versus control, suggesting that NNS consumption altered body fat distribution.

Inulin fiber dose-dependently modulates energy balance, glucose tolerance, gut microbiota, hormones and diet preference in high-fat-fed male rats

2018 ◽  
Vol 59 ◽  
pp. 142-152 ◽  
Author(s):  
Arashdeep Singh ◽  
Rizaldy C. Zapata ◽  
Adel Pezeshki ◽  
Roger D. Reidelberger ◽  
Prasanth K. Chelikani
Keyword(s):  
Energy Balance ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Male Rats ◽  
High Fat ◽  
Diet Preference

scholarly journals Maternal Choline Supplementation During Gestational Diabetes Causes Long-Term Phenotypic Changes in Offspring (P11-132-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hunter Korsmo ◽  
Kaydine Edwards ◽  
Bhoomi Dave ◽  
Chauntelle Jack-Roberts ◽  
Xinyin Jiang
Keyword(s):  
New York ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Control Diet ◽  
Fasting Blood Glucose ◽  
Blood Glucose Control ◽  
Female Offspring ◽  
Male Offspring ◽  
York Academy

Abstract Objectives Using a mouse gestational diabetes mellitus (GDM) model, this study investigated whether maternal choline supplementation (MCS) could alter postnatal growth and metabolic abnormalities associated with GDM. Methods C57BL/6 mice were either fed a low fat (LF, 10kcal % fat) control diet or a high fat (HF, 60kcal % fat) diet prior to and during pregnancy to induce GDM. These mice received either 25mM choline (MCS) or plain drinking water, After weaning, offspring were fed the HF diet for 6 weeks before glucose tolerance testing and dissection. Results In male offspring from MCS-GDM mothers, we observed a decrease in fasting blood glucose levels and an increase in glucose tolerance when comparing to other groups (P < 0.05). Liver choline metabolite measurements demonstrated that free choline content was lower (P = 0.01) in the MCS-GDM male offspring than control GDM male offspring; there is also an increase in liver sphingomyelin concentrations (P = 0.007) in female offspring from MCS-GDM compared to control GDM dams. Conclusions MCS during GDM leads to improvements in blood glucose control in male mouse offspring exposed to a postnatal HF environment. Funding Sources NIGMS and NIDDK; New York Academy of Sciences.

scholarly journals The Effect of Neonatal Leptin Treatment on Postnatal Weight Gain in Male Rats Is Dependent on Maternal Nutritional Status during Pregnancy

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1906-1913 ◽  
Author(s):  
Mark H. Vickers ◽  
Peter D. Gluckman ◽  
Alice H. Coveny ◽  
Paul L. Hofman ◽  
Wayne S. Cutfield ◽  
...  
Keyword(s):  
Weight Gain ◽  
Nutritional Status ◽  
Energy Homeostasis ◽  
Caloric Intake ◽  
Developmental Trajectory ◽  
Male Offspring ◽  
Male Rats ◽  
Metabolic Phenotype ◽  
Chow Diet

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this “programming” has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Using this model of maternal UN, we have recently shown that neonatal leptin treatment in females reverses the postnatal sequelae induced by developmental programming. To examine possible gender-related effects of neonatal leptin treatment, the present study investigated the effect of neonatal leptin treatment on the metabolic phenotype of adult male offspring. Leptin treatment (recombinant rat leptin, 2.5 μg/g·d, sc) from postnatal d 3–13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring. Neonatal leptin treatment of male offspring from normally nourished mothers caused an increase in diet-induced weight gain and related metabolic sequelae, including hyperinsulinemia and increased total body adiposity compared with saline-treated controls. This occurred without an increase in caloric intake. These effects were specific to offspring of normal pregnancies and were not observed in offspring of mothers after UN during pregnancy. In the latter, neonatal leptin treatment conferred protection against the development of the programmed phenotype, particularly in those fed the chow diet postnatally. These data further reinforce the importance of leptin in determining long-term energy homeostasis, and suggest that leptin’s effects are modulated by gender and both prenatal and postnatal nutritional status.

scholarly journals Maternal feeding patterns affect the offspring’s brain: focus on serotonin 5-HT2C and 5-HT2A receptors

2021 ◽  
Author(s):  
Kinga Gawlińska ◽  
Dawid Gawliński ◽  
Małgorzata Filip ◽  
Edmund Przegaliński
Keyword(s):  
Maternal Diet ◽  
Dorsal Striatum ◽  
Wistar Rat ◽  
Female Offspring ◽  
Receptor Expression ◽  
Mental Illnesses ◽  
Male Offspring ◽  
Female Rats ◽  
Male Rats ◽  
Adolescent Male

Abstract Background Recent studies have shown a relationship between the composition of the maternal diet and acquiring a risk of mental illnesses through changes in the offspring’s brain. This study assessed the role of a modified maternal diet on the levels of serotonin (5-HT)2C and 5-HT2A receptors in the offspring brain. Methods Wistar rat dams during gestation and lactation were maintained either on a standard (SD) or special diets: high-fat (HFD), high-carbohydrate (rich in sucrose, HCD) or mixed (MD). Offspring were weaned to SD after lactation, and at postnatal days (PNDs) 28 and 63 changes in the 5-HT2C and 5-HT2A receptor levels were evaluated in their prefrontal cortex (PFCx), nucleus accumbens (NAc), dorsal striatum (DSTR) and hippocampus (HIP). Results Maternal HFD reduced the expression of 5-HT2C receptors in male rats at PND 28 in the PFCx, NAc, and DSTR but increased it at PND 63 in male animals in the NAc and DSTR. HCD induced a decrease in the expression of 5-HT2C receptors in male offspring at PND 28 but increased it in female rats at PND 63 in the PFCx. MD reduced 5-HT2C receptor expression in males at PND 28 in the PFCx and increased it in male and female offspring at PND 28 in the HIP. Moreover, maternal HFD reduced 5-HT2A receptor levels within the PFCx in adolescent male offspring. Conclusion Our findings indicate that a modified maternal diet induces age- and sex-specific adaptive changes mainly in 5-HT2C receptors, which may contribute to disturbances in the offspring brain. Graphic abstract

The long-acting amylin/calcitonin receptor agonist ZP5461 suppresses food intake and body weight in male rats

2021 ◽  
Author(s):  
Lauren M. Stein ◽  
Lauren E McGrath ◽  
Rinzin Lhamo ◽  
Kieran Koch-Laskowski ◽  
Samantha M. Fortin ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Intake ◽  
Receptor Agonist ◽  
Body Weight Gain ◽  
Male Rats ◽  
Calcitonin Receptor ◽  
Long Acting

The peptide hormone amylin reduces food intake and body weight, and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds' potential utility in promoting sustained negative energy balance. Here, we evaluate the ability of the novel long-acting amylin/calcitonin receptor agonist ZP5461 to reduce feeding and body weight in rats, and also test the role of calcitonin receptors (CTRs) in the dorsal vagal complex (DVC) of the hindbrain in the energy balance effects of chronic ZP5461 administration. Acute dose-response studies indicate that systemic ZP5461 (0.5-3 nmol/kg) robustly suppresses energy intake and body weight gain in chow- and high-fat diet (HFD)-fed rats. When HFD-fed rats received chronic systemic administration of ZP5461 (1-2 nmol/kg), the compound initially produced reductions in energy intake and weight gain, but failed to produce sustained suppression of intake and body weight. Using virally-mediated knockdown of DVC CTRs, the ability of chronic systemic ZP5461 to promote early reductions in intake and body weight gain was determined to be mediated in part by activation of DVC CTRs, implicating the DVC as a central site of action for ZP5461. Future studies should address other dosing regimens of ZP5461 to determine whether an alternative dose/frequency of administration would produce more sustained body weight suppression.

scholarly journals β-Endorphin Antagonizes the Effects of α-MSH on Food Intake and Body Weight

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4246-4255 ◽  
Author(s):  
Roxanne Dutia ◽  
Kana Meece ◽  
Shveta Dighe ◽  
Andrea J. Kim ◽  
Sharon L. Wardlaw
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Food Intake ◽  
Body Weight Gain ◽  
Male Rats ◽  
Negative Effects ◽  
Entire Study ◽  
Peptide Interactions ◽  
Model Weight

Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injection of β-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv β-EP infusion. In the next study, a subthreshold dose of β-EP was injected together with Nle4, d-Phe7 (NDP)-MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of β-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4–7, β-EP no longer blocked these effects. Of note, the stimulatory effect of β-EP on feeding and its ability to antagonize MSH were specific for β-EP1–31 and were not observed with β-EP1–27. This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance.

Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats

1989 ◽  
Vol 66 (4) ◽  
pp. 1970-1975 ◽  
Author(s):  
J. Arnold ◽  
R. A. Little ◽  
N. J. Rothwell
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Male Rats ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9811
Author(s):  
Edward T. Wargent ◽  
Malgorzata Kepczynska ◽  
Mohamed Sghaier Zaibi ◽  
David C. Hislop ◽  
Jonathan R.S. Arch ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Insulin Tolerance

Background The insulin-sensitizing phytocannabinoid, Δ(9)-tetrahydrocannabivarin (THCV) can signal partly via G-protein coupled receptor-55 (GPR55 behaving as either an agonist or an antagonist depending on the assay). The cannabinoid receptor type 1 (CB1R) inverse agonist rimonabant is also a GPR55 agonist under some conditions. Previous studies have shown varied effects of deletion of GPR55 on energy balance and glucose homeostasis in mice. The contribution of signalling via GPR55 to the metabolic effects of THCV and rimonabant has been little studied. Methods In a preliminary experiment, energy balance and glucose homeostasis were studied in GPR55 knockout and wild-type mice fed on both standard chow (to 20 weeks of age) and high fat diets (from 6 to 15 weeks of age). In the main experiment, all mice were fed on the high fat diet (from 6 to 14 weeks of age). In addition to replicating the preliminary experiment, the effects of once daily administration of THCV (15 mg kg−1 po) and rimonabant (10 mg kg−1 po) were compared in the two genotypes. Results There was no effect of genotype on absolute body weight or weight gain, body composition measured by either dual-energy X-ray absorptiometry or Nuclear Magnetic Resonance (NMR), fat pad weights, food intake, energy expenditure, locomotor activity, glucose tolerance or insulin tolerance in mice fed on chow. When the mice were fed a high fat diet, there was again no effect of genotype on these various aspects of energy balance. However, in both experiments, glucose tolerance was worse in the knockout than the wild-type mice. Genotype did not affect insulin tolerance in either experiment. Weight loss in rimonabant- and THCV-treated mice was lower in knockout than in wild-type mice, but surprisingly there was no detectable effect of genotype on the effects of the drugs on any aspect of glucose homeostasis after taking into account the effect of genotype in vehicle-treated mice. Conclusions Our two experiments differ from those reported by others in finding impaired glucose tolerance in GPR55 knockout mice in the absence of any effect on body weight, body composition, locomotor activity or energy expenditure. Nor could we detect any effect of genotype on insulin tolerance, so the possibility that GPR55 regulates glucose-stimulated insulin secretion merits further investigation. By contrast with the genotype effect in untreated mice, we found that THCV and rimonabant reduced weight gain, and this effect was in part mediated by GPR55.

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