Glucosamine Enhances Body Weight Gain and Reduces Insulin Response in Mice Fed Chow Diet but Mitigates Obesity, Insulin Resistance and Impaired Glucose Tolerance in Mice High-Fat Diet

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.

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Dietary Cyanidin-3-Glucoside Attenuates High-Fat-Diet–Induced Body-Weight Gain and Impairment of Glucose Tolerance in Mice via Effects on the Hepatic Hormone FGF21

Journal of Nutrition ◽

10.1093/jn/nxaa140 ◽

2020 ◽

Vol 150 (8) ◽

pp. 2101-2111 ◽

Cited By ~ 1

Author(s):

Lili Tian ◽

Hongmei Ning ◽

Weijuan Shao ◽

Zhuolun Song ◽

Yasaman Badakhshi ◽

...

Keyword(s):

Drinking Water ◽

Body Weight ◽

Weight Gain ◽

Glucose Tolerance ◽

High Fat Diet ◽

Body Weight Gain ◽

Fibroblast Growth Factor 21 ◽

High Fat ◽

Beneficial Effects ◽

Fgf21 Expression

ABSTRACT Background Dietary polyphenols including anthocyanins target multiple organs. Objective We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G). Methods Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.6 mg Cy3G/L in drinking water for 3 wk [experiment (Exp.) 1; n = 5/group]. Similar mice were fed the LFD or a high-fat diet (HFD; 60% energy from fat) with or without Cy3G for 20 wk. Half of the mice administered Cy3G also received 4 broad-spectrum antibiotics (ABs) in drinking water between weeks 11 and 14, for a total of 6 groups (n = 8/group). Metabolic tolerance tests were conducted between weeks 2 and 16. Relevant hormone gene expression and plasma hormone concentrations were assessed mainly at the end of 20 wk (Exp. 2). Results In Exp. 1, Cy3G administration increased ileal but not colonic Gcg level by 2-fold (P < 0.05). In Exp. 2, Cy3G attenuated HFD-induced body-weight gain (20.3% at week 16), and improved glucose tolerance (26.5% at week 15) but not insulin tolerance. Although Cy3G had no effect on glucose tolerance in LFD mice, LFD/Cy3G/AB mice showed better glucose tolerance than LFD/Cy3G mice (23%). In contrast, HFD/Cy3G/AB mice showed worse glucose tolerance compared with HFD/Cy3G mice (15%). Beneficial effects of Cy3G in HFD mice were not associated with changes in plasma leptin, insulin or GLP-1 concentrations. However, Cy3G increased hepatic Fgf21 expression in mice in Exp. 1 by 4-fold and attenuated Fgf21 overexpression in HFD mice (Exp. 2, 22%), associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05). Conclusions Dietary Cy3G may reduce body weight and exert metabolic homeostatic effects in mice via changes in hepatic FGF21.

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

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.34.1257 ◽

2011 ◽

Vol 34 (8) ◽

pp. 1257-1263 ◽

Cited By ~ 18

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

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Genetic deletion of soluble 5′-nucleotidase II reduces body weight gain and insulin resistance induced by a high-fat diet

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2019.01.017 ◽

2019 ◽

Vol 126 (4) ◽

pp. 377-387 ◽

Cited By ~ 3

Author(s):

Manuel Johanns ◽

Samanta Kviklyte ◽

Sheng-Ju Chuang ◽

Katrien Corbeels ◽

Roxane Jacobs ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

High Fat ◽

Genetic Deletion

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Soy Protein Health Benefits Are in Part Dependent of the Gut Microbiota

Current Developments in Nutrition ◽

10.1093/cdn/nzaa049_062 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 669-669

Author(s):

Armando Tovar ◽

Monica Sanchez-Tapia ◽

Daniela Moreno ◽

Guillermo Ordaz ◽

Martha Guevara ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Energy Expenditure ◽

Glucose Tolerance ◽

Gut Microbiota ◽

Antibiotic Treatment ◽

Soy Protein ◽

High Fat Diet ◽

Body Weight Gain ◽

High Fat

Abstract Objectives Several studies have demonstrated that the consumption of soy protein decreases LDL-cholesterol, improves insulin sensitivity and attenuates body weight gain. Also, soy protein consumption can modify the gut microbiota, however it has not been established whether the changes in gut microbiota are in part responsible of the health effects of soy protein. Thus, the aim of the present study was to understand whether the metabolic effects of soy protein are reduced by the use of an antibiotic treatment. Methods Rats were fed for 16 weeks with one of the 4 experimental diets: 1) Casein control diet (C), 2) Soy protein diet (S), 3) C high-fat diet, and 4) S high-fat diet. Each group was sub-divided at the end of the 16 weeks in 2 groups. One subgroup continue with the same diet, and the other received the antibiotic treatment (Ampicillin/Neomycin) for 4 weeks. During the study body weight, food intake, body composition, energy expenditure and glucose tolerance were measured. Fecal samples were collected before and after the antibiotic treatment to determine the gut microbiota using the Illumina platform. At the end of the study blood samples were obtained to measure several biochemical variables. Also, liver and adipose tissue samples were obtained to assess the abundance of mRNA and proteins involved in lipid, glucose and thermogenesis. Results Rats fed S or S high fat diet had significant lower body weight gain, body fat, energy expenditure, glucose tolerance, blood lipids, increased expression of thermogenic genes and decreased serum lipopolisacharide than the control or high fat groups fed C diets. The antibiotic treatment abolished the health benefits observed in rats fed the S diets, particularly energy expenditure and weight gain. These changes were associated with changes in the gut microbiota, since S consumption increased the abundance of the Akkermansia and Bifidobacterium genus. This effect on the gut microbiota was prevented by the antibiotic treatment and rats developed metabolic endotoxemia. Finally, the antibiotic treatment reduced the expression of thermogenic genes, particularly in rats fed S high fat diet. Conclusions This study indicates that the beneficial effects of soy protein consumption on health are significantly dependent on the gut microbiota. Funding Sources CONACYT, INCMNSZ.

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A multispecies Lactobacillus- and Bifidobacterium-containing probiotic mixture attenuates body weight gain and insulin resistance after a short-term challenge with a high-fat diet in C57/BL6J mice

PharmaNutrition ◽

10.1016/j.phanu.2015.03.003 ◽

2015 ◽

Vol 3 (3) ◽

pp. 101-107 ◽

Cited By ~ 10

Author(s):

Sophie Holowacz ◽

Charlotte Guigné ◽

Gérald Chêne ◽

Sandrine Mouysset ◽

Angèle Guilbot ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

High Fat ◽

Short Term

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RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance

Pharmaceuticals ◽

10.3390/ph14111178 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1178

Author(s):

Gabsik Yang ◽

Hye Eun Lee ◽

Jin Kyung Seok ◽

Han Chang Kang ◽

Yong-Yeon Cho ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Er Stress ◽

High Fat Diet ◽

Metabolic Disorders ◽

Body Weight Gain ◽

Metabolic Stress ◽

Normal Diet ◽

High Fat

Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.

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Novel human resistin antagonist (monomeric C6A mutant) reduced body weight gain and restored insulin responsiveness in mice fed high fat diet

Endocrine Abstracts ◽

10.1530/endoabs.37.gp.15.04 ◽

2015 ◽

Author(s):

Yacir Benomar ◽

Gili Solomon ◽

Hamza Amine ◽

Ahlem Othmane ◽

Arieh Gertler ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

High Fat ◽

Reduced Body ◽

Insulin Responsiveness ◽

Human Resistin

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Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22105390 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5390

Author(s):

Qianhui Zeng ◽

Nannan Wang ◽

Yaru Zhang ◽

Yuxuan Yang ◽

Shuangshuang Li ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Insulin Sensitivity ◽

Energy Metabolism ◽

Glucose Tolerance ◽

High Fat Diet ◽

Chow Diet ◽

High Fat ◽

Glycolipid Metabolism ◽

Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

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