Effects of combined glucocorticoid/mineralocorticoid receptor modulation (CORT118335) on energy balance, adiposity, and lipid metabolism in male rats

2019 ◽  
Vol 317 (2) ◽  
pp. E337-E349
Author(s):  
Elizabeth T. Nguyen ◽  
Sarah Berman ◽  
Joshua Streicher ◽  
Christina M. Estrada ◽  
Jody L. Caldwell ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
The Body ◽  
Male Rats ◽  
Chow Diet ◽  
High Fat ◽  
Receptor Modulation

Psychological stress and excess glucocorticoids are associated with metabolic and cardiovascular diseases. Glucocorticoids act primarily through mineralocorticoid (MR) and glucocorticoid receptors (GR), and compounds modulating these receptors show promise in mitigating metabolic and cardiovascular-related phenotypes. CORT118335 (GR/MR modulator) prevents high-fat diet-induced weight gain and adiposity in mice, but the ability of this compound to reverse obesity-related symptoms is unknown. Adult male rats were subcutaneously administered CORT118335 (3, 10, or 30 mg/kg) or vehicle once daily. A 5-day treatment with CORT118335 at 30 mg/kg induced weight loss in rats fed a chow diet by decreasing food intake. However, lower doses of the compound attenuated body weight gain primarily because of decreased calorific efficiency, as there were no significant differences in food intake compared with vehicle. Notably, the body weight effects of CORT118335 persisted during a 2-wk treatment hiatus, suggesting prolonged effects of the compound. To our knowledge, we are the first to demonstrate a sustained effect of combined GR/MR modulation on body weight gain. These findings suggest that CORT118335 may have long-lasting effects, likely due to GR/MR-induced transcriptional changes. Prolonged (18 days) treatment of CORT118335 (10 mg/kg) reversed body weight gain and adiposity in animals fed a high-fat diet for 13 wk. Surprisingly, this occurred despite a worsening of the lipid profile and glucose homeostasis as well as a disrupted diurnal corticosterone rhythm, suggesting GR agonistic effects in the periphery. We conclude that species and tissue-specific targeting may result in promising leads for exploiting the metabolically beneficial aspects of GR/MR modulation.

scholarly journals The Effects of Triacylglycerol Structures on the Food Intake and Body Weight of Mice in a High-Fat Diet Setting

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1216-1216
Author(s):  
Xinge Hu
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
High Fat Diet ◽  
Tissue Sample ◽  
Body Weight Gain ◽  
Diet Group ◽  
The Body ◽  
Lower Percentage ◽  
Chow Diet ◽  
High Fat

Abstract Objectives The dietary fat content plays an important role in the regulation of chronic metabolic diseases such as obesity and type 2 diabetes. Here, we tested the impacts of triacylglycerol structure on the body weight gain and food intake of mice in a high-fat diet (HFD) setting. Methods Male C57/BL6J mice at 6 weeks old were fed one of the following three diets for 6 weeks, Teklad Rodent Diet chow diet (number 8640), the chow diet containing 36% (w/w) 1,2-Dipalmitoyl-3-oleoylglycerol (PPO), or the chow diet containing 36% (w/w) 1,3-Dipalmitoyl-2-oleoylglycerol (POP). Each group contained 9 mice, and their food intake and BW were measured daily. The mice were euthanized after 6 weeks (12 weeks old) for tissue sample collection. Results Both high HFD groups had significantly higher BW gain and caloric intakes than the chow diet group. Mice fed the POP diet had a lower percentage of BW gain and consumed less accumulated calories than those fed the PPO diet, as well as a significantly lower liver to BW ratio. Since week 4, the body BW rate of the POP group started to be lower than that of the PPO diet group. Conclusions TAG structures in an HFD setting affect the BW gain rate and obesity in mice. The different structures of fat added to affect the food intake and BW gain differently in an HFD setting. In the future, we would like to compare the changes of the hepatic lipogenesis enzyme in these mice. This will help us to understand how the triacylglycerol structures in the diet affect lipid metabolism in mice. Funding Sources Internal.

scholarly journals A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2504
Author(s):  
Raquel Urtasun ◽  
Joana Díaz-Gómez ◽  
Miriam Araña ◽  
María José Pajares ◽  
María Oneca ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Bacillus Coagulans ◽  
Normal Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Traditional Remedy

Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.

scholarly journals Rhythmic neuronal activities of the rat nucleus of the solitary tract are impaired by short-term high fat diet - implications for daily control of satiety by the brainstem

2021 ◽  
Author(s):  
Lukasz Chrobok ◽  
Jasmin D Klich ◽  
Anna M Sanetra ◽  
Jagoda S Jeczmien-Lazur ◽  
Kamil Pradel ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Circadian Rhythms ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Solitary Tract ◽  
High Fat ◽  
Short Term ◽  
Extrinsic Factors

ABSTRACTTemporal partitioning of daily food intake is crucial for survival and involves the integration of internal circadian states and external influences such as the light-dark cycle and the composition of diet. These intrinsic and extrinsic factors are interdependent with misalignment of circadian rhythms promoting body weight gain, while consumption of a calorie dense diet elevates the risk of obesity and blunts circadian rhythms. Since cardiovascular disease, metabolic disorders, and cancer are comorbid with obesity, understanding the relationships between brain activity and diet is of pivotal importance. Recently, we defined for the first time the circadian properties of the dorsal vagal complex of the brainstem, a structure implicated in the control of food intake and autonomic tone, but if and how 24 h rhythms in this area are influenced by diet remains unresolved. Here we focused on a key structure of this complex, the nucleus of the solitary tract, and using a range of approaches, we interrogated how its neuronal and cellular rhythms are affected by high-fat diet. We report that short term consumption of this diet increases food intake during the day and blunts daily rhythms in gene expression and neuronal discharge in the nucleus of the solitary tract. These alterations in this structure occur without prominent body weight gain, suggesting that high-fat diet acts initially to reduce activity in the nucleus of the solitary tract, thereby disinhibiting mechanisms that suppress daytime feeding.GRAPHICAL ABSTRACT

scholarly journals Effectiveness ofCoelatura aegyptiacaExtract Combination with Atorvastatin on Experimentally Induced Hyperlipidemia in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ayman Saber Mohamed ◽  
Walaa Mohammed Ibrahim ◽  
Nashwah Ismail Zaki ◽  
Sara Bayoumi Ali ◽  
Amel M. Soliman
Keyword(s):  
Body Weight ◽  
Uric Acid ◽  
Antioxidant System ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
The Body ◽  
Male Rats ◽  
High Fat ◽  
Total Proteins ◽  
Group Control

Background. The present study aimed to assess the effectiveness of clam extract in combination with atorvastatin against experimentally hyperlipidemia in rats.Method. Forty male rats were divided into 5 groups (8 rats /group): control, high fat diet (HFD), atorvastatin (AROR), clam extract (CE), and ATOR + CE.Results. The treatments with ATOR and /or CE significantly reduced the body weight gain, AST, ALT, ALP, TL, TC, TG, LDL-C, urea, creatinine, and uric acid levels while they increased total proteins, albumin, and HDL-C. The treatment with ATOR only did not cause any significant change in CK and MDA along with antioxidant system, while the treatment with CE alone or with ATOR significantly decreased CK and MDA accompanied by improving the antioxidant system.Conclusion. Combination of CE extract with atorvastatin improved the hyperlipidemic efficacy and reduced undesirable side effects especially on muscle.

scholarly journals Factor for Adipocyte Differentiation 158 Gene Disruption Prevents the Body Weight Gain and Insulin Resistance Induced by a High-Fat Diet

2011 ◽  
Vol 34 (8) ◽  
pp. 1257-1263 ◽  
Author(s):  
Takahiro Hayashi ◽  
Yuriko Nozaki ◽  
Makoto Nishizuka ◽  
Masahito Ikawa ◽  
Shigehiro Osada ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Gene Disruption ◽  
Adipocyte Differentiation ◽  
Body Weight Gain ◽  
The Body ◽  
High Fat

Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight

2007 ◽  
Vol 293 (5) ◽  
pp. R1855-R1863 ◽  
Author(s):  
Christine Mack ◽  
Julie Wilson ◽  
Jennifer Athanacio ◽  
James Reynolds ◽  
Kevin Laugero ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Locomotor Activity ◽  
Food Intake ◽  
Energy Expenditure ◽  
Food Preference ◽  
Body Weight Gain ◽  
The Body ◽  
High Fat

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4–11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3–300 μg·kg−1·day−1) dose dependently reduced food intake and body weight gain (ED50for body weight gain = 16.5 μg·kg−1·day−1). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 μg·kg−1·day−1) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 μg·kg−1·day−1) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.

scholarly journals Biochemical and Physiological Parameters in Rats Fed with High-Fat Diet: The Protective Effect of Chronic Treatment with Purple Grape Juice (Bordo Variety)

Beverages ◽  
2018 ◽  
Vol 4 (4) ◽  
pp. 100 ◽  
Author(s):  
Denise dos Santos Lacerda ◽  
Mariana Garbin de Almeida ◽  
Cláudia Teixeira ◽  
Alyne de Jesus ◽  
Édison da Silva Pereira Júnior ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Protective Effect ◽  
High Fat Diet ◽  
Grape Juice ◽  
Abdominal Fat ◽  
The Body ◽  
Male Rats ◽  
High Fat ◽  
Grape Juices

High-fat-diet (HFD) has been related to metabolic and cardiovascular diseases. Consumption of grapes and their byproducts containing phenolic compounds has been reported due to the benefits they produce for human health. The purpose of this study was to investigate the antioxidant and protective effect of chronic intake of purple grape juice on certain biochemical and physiological changes promoted by the consumption of HFD. Forty male rats were randomly divided into four groups to receive standard or HFD diet and/or conventional (CGJ) or organic grape juice (OGJ) for three months. Dietary intake, body weight gain, cardiometabolic parameters, and serum lipoperoxidation were investigated. Results showed that consumption of CGJ and OGJ changed the pattern of food and drink intake of the animals. There was a reduction in the body weight of animals that consumed grape juices and an increase in the weight gain in HFD and OGJ rats. HFD increased abdominal fat and the abdominal fat/weight ratio, and both grape juices prevented these modifications. HFD increased hepatic enzymes levels (aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)) and reduced urea. Purple grape juices prevented some of these changes. HFD enhanced lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) in serum and CGJ and OGJ prevented this increase. The consumption of purple grape juice has the potential to prevent and ameliorate most of the alterations provoked by HFD, therefore regular intake of grape products could promote beneficial effects.

Abstract 75: Chronic Treatment With At2 Receptor Agonist Rescues High Fat Diet-induced Obesity in Female Mice.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Mohammed A Khan ◽  
Preethi Samuel ◽  
Sourashish Nag ◽  
Tahir Hussain
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
The Body ◽  
Calorie Intake ◽  
Adipocyte Size ◽  
High Fat ◽  
Female Mice ◽  
Diet Induced Obesity

Obesity in itself is a disease condition and a major risk factor in the development of hypertension, dyslipidemia, and hyperglycemia. Therefore, successful strategies for improving obesity and related metabolic risk factors are needed. Role of renin-angiotensin system (RAS) has been implicated in obesity and metabolic dysfunction. Recently, we have shown that AT2R knock-out in female mice caused a greater body weight gain and hyperinsulimia in response to high fat diet (HFD). In the present study, we hypothesize that AT2R activation rescues diet-induced obesity in females. To test this hypothesis, we injected AT2R non-peptide agonist C21 (0.3mg/kg/day i.p) in C57BL6 female mice on HFD for 12 weeks. C21-treatment did not affect the HFD calorie intake (HFD: 937±18 Kcal; C21HFD: 886±37 Kcal) but caused lesser body weight gain compared to control (HFD: 4.4± 0.4g; C21HFD: 3.06± 0.4g). Similar to the body weight gain pattern, gonadal fat weight and adipocyte size were decreased significantly in C21-treated mice on HFD compared to control HFD group (HFD: 4.4± 0.4 g; C21 HFD: 3.06± 0.4g) and (HFD: 6404±161.6μm2 ; C21HFD: 3874±103.2μm2 ) respectively. Moreover, the C21-treated females on HFD had lower levels of plasma insulin, improved glucose tolerance, and decreased plasma free fatty acids and hepatic triglycerides. Western blot revealed that phospho-Ser79-acetyl CoA carboxylase (p-Ser79-ACC-1) was reduced, an index of increased lipogenic activity and decreased β-oxidation process, in both adipose (Adi) and hepatic (Hep) tissues of HFD fed groups (Adi: 86% and Hep: 73% of 100% controls); C21-treatment revered the decrease in p-ser79-ACC-1 in Adi (104% of control) and caused an increase in Hep (122% of control) respectively. The HFD feeding lowered the estradiol level (ND: 38.8±2.6 vs HFD:11.3±1.2ng), which was modestly reversed by C21 treatment (C21HFD:17.4± 1.5ng) in HFD mice. Our results strongly suggest that stimulation of AT2R in female mice positively contribute, predominantly independent of estrogen, to rescue body weight gain and adipocyte size increase in response to HFD. We propose reduced lipogenesis and enhanced lipid β-oxidation as potential mechanisms linked to AT2R action in reducing obesity and its related metabolic disorders in females.

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