Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice

Abstract Background The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. Methods Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. Results Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-β/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. Conclusions These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

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Bofutsushosan, an Oriental Herbal Medicine, Attenuates the Weight Gain of White Adipose Tissue and the Increased Size of Adipocytes Associated with the Increase in Their Expression of Uncoupling Protein 1 in High-Fat Diet-Fed Male KK/Ta mice

Journal of Clinical Biochemistry and Nutrition ◽

10.3164/jcbn.2008023 ◽

2008 ◽

Vol 42 (2) ◽

pp. 158-166 ◽

Cited By ~ 30

Author(s):

Satomi Akagiri ◽

Yuji Naito ◽

Hiroshi Ichikawa ◽

Katsura Mizushima ◽

Tomohisa Takagi ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Herbal Medicine ◽

White Adipose Tissue ◽

High Fat Diet ◽

Uncoupling Protein ◽

High Fat ◽

Uncoupling Protein 1

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Weight Gain, Glucose Tolerance, and the Gut Microbiome of Male C57BL/6J Mice Housed on Corncob or Paper Bedding and Fed Normal or High-Fat Diet

Journal of the American Association for Laboratory Animal Science ◽

10.30802/aalas-jaalas-20-000139 ◽

2021 ◽

Author(s):

Mohammed R Islam ◽

Kimberly A Schultz ◽

Mita Varghese ◽

Simin H Abrishami ◽

Jason S Villano ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

White Adipose Tissue ◽

Gut Microbiome ◽

High Fat Diet ◽

Animal Husbandry ◽

Normal Diet ◽

High Fat ◽

16S Sequencing ◽

Similar Body

Understanding how differences in animal husbandry practices affect the reproducibility of research results is critical. Wesought to understand how different beddings might influence dietary obesity studies. We compared the effects of paper andcorncob bedding on weight gain, metabolism, and gut microbiome (GM) of mice fed a high-fat diet (HFD) or a normal diet(ND) and evaluated effects on fecal and cecal microbiomes collected from these cohorts after euthanasia. Male C57BL/6J mice at 5 wk age were allowed to acclimate to the facility and the assigned bedding for one week before being placed on HFD or remaining on the ND for 12 wk. Fecal pellets and cecal samples were collected and frozen for batched 16S sequencing. Mice had similar body weight, visceral gonadal white adipose tissue (GWAT), subcutaneous inguinal white adipose tissue (IWAT), liver and spleen weights and metabolic changes regardless of the bedding type. Baseline microbiota differences were detected one week after bedding assignment. After 12 wk, the GM showed significant differences depending on both bedding and diet. The effects of the bedding were not significantly different between endpoint fecal and cecal GM, despite the inherent differences in microbiota in fecal and cecal samples. A correlation was detected between diet and the relative abundance of Bacteroidetes and Verrucomicrobia:Akkermansia. In conclusion, this study demonstrates the importance of considering bedding type when performing dietary experiments.

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Lyophilized Maqui (Aristotelia chilensis) Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice

Antioxidants ◽

10.3390/antiox8090360 ◽

2019 ◽

Vol 8 (9) ◽

pp. 360 ◽

Cited By ~ 6

Author(s):

Viviana Sandoval ◽

Antoni Femenias ◽

Úrsula Martínez-Garza ◽

Hèctor Sanz-Lamora ◽

Juan Castagnini ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Binding Protein ◽

Fibroblast Growth Factor 21 ◽

Obese Mice ◽

High Fat ◽

Subcutaneous White Adipose Tissue ◽

Aristotelia Chilensis

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

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Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice

Endocrinology ◽

10.1210/en.2015-1588 ◽

2015 ◽

Vol 157 (3) ◽

pp. 1029-1042 ◽

Cited By ~ 66

Author(s):

Atsushi Obata ◽

Naoto Kubota ◽

Tetsuya Kubota ◽

Masahiko Iwamoto ◽

Hiroyuki Sato ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Glucose Uptake ◽

White Adipose Tissue ◽

High Fat Diet ◽

Molecular Mechanisms ◽

The Body ◽

High Fat ◽

Ad Libitum

Abstract Sodium glucose cotransporter 2 inhibitors have attracted attention as they exert antidiabetic and antiobesity effects. In this study, we investigated the effects of tofogliflozin on glucose homeostasis and its metabolic consequences and clarified the underlying molecular mechanisms. C57BL/6 mice were fed normal chow containing tofogliflozin (0.005%) for 20 weeks or a high-fat diet containing tofogliflozin (0.005%) for 8 weeks ad libitum. In addition, the animals were pair-fed in relation to controls to exclude the influence of increased food intake. Tofogliflozin reduced the body weight gain, mainly because of fat mass reduction associated with a diminished adipocyte size. Glucose tolerance and insulin sensitivity were ameliorated. The serum levels of nonesterified fatty acid and ketone bodies were increased and the respiratory quotient was decreased in the tofogliflozin-treated mice, suggesting the acceleration of lipolysis in the white adipose tissue and hepatic β-oxidation. In fact, the phosphorylation of hormone-sensitive lipase and the adipose triglyceride lipase protein levels in the white adipose tissue as well as the gene expressions related to β-oxidation, such as Cpt1α in the liver, were significantly increased. The hepatic triglyceride contents and the expression levels of lipogenic genes were decreased. Pair-fed mice exhibited almost the same results as mice fed an high-fat diet ad libitum. Moreover, a hyperinsulinemic-euglycemic clamp revealed that tofogliflozin improved insulin resistance by increasing glucose uptake, especially in the skeletal muscle, in pair-fed mice. Taken together, these results suggest tofogliflozin ameliorates insulin resistance and obesity by increasing glucose uptake in skeletal muscle and lipolysis in adipose tissue.

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No Additive Effects of Polyphenol Supplementation and Exercise Training on White Adiposity Determinants of High-Fat Diet-Induced Obese Insulin-Resistant Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7406946 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Karen Lambert ◽

Marie Hokayem ◽

Claire Thomas ◽

Odile Fabre ◽

Cécile Cassan ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Exercise Training ◽

White Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Insulin Resistant ◽

Polyphenol Intake ◽

Tissue Alterations

One of the major insulin resistance instigators is excessive adiposity and visceral fat depots. Individually, exercise training and polyphenol intake are known to exert health benefits as improving insulin sensitivity. However, their combined curative effects on established obesity and insulin resistance need further investigation particularly on white adipose tissue alterations. Therefore, we compared the effects on different white adipose tissue depot alterations of a combination of exercise and grape polyphenol supplementation in obese insulin-resistant rats fed a high-fat diet to the effects of a high-fat diet alone or a nutritional supplementation of grape polyphenols (50 mg/kg/day) or exercise training (1 hr/day to 5 days/wk consisting of treadmill running at 32 m/min for a 10% slope), for a total duration of 8 weeks. Separately, polyphenol supplementation and exercise decreased the quantity of all adipose tissue depots and mesenteric inflammation. Exercise reduced adipocytes’ size in all fat stores. Interestingly, combining exercise to polyphenol intake presents no more cumulative benefit on adipose tissue alterations than exercise alone. Insulin sensitivity was improved at systemic, epididymal, and inguinal adipose tissues levels in trained rats thus indicating that despite their effects on adipocyte morphological/metabolic changes, polyphenols at nutritional doses remain less effective than exercise in fighting insulin resistance.

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Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00245.2006 ◽

2007 ◽

Vol 292 (4) ◽

pp. E1079-E1086 ◽

Cited By ~ 99

Author(s):

John W. Bullen ◽

Susann Bluher ◽

Theodoros Kelesidis ◽

Christos S. Mantzoros

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Energy Homeostasis ◽

High Fat ◽

Diet Induced Obesity ◽

Adiponectin Mrna ◽

Obesity In Mice ◽

Fat Feeding

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

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Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome-induced rats

10.1101/459610 ◽

2018 ◽

Author(s):

Marwa El-Zeftawy ◽

Doaa Ghareeb ◽

Rasha Saad ◽

Salma Mahmoud ◽

Nihal Elguindy ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Lipid Profiles ◽

Dependent Diabetes Mellitus ◽

Model Assessment ◽

High Fat ◽

Berberine Chloride

AbstractInsulin resistance is one of dangerous factors as it leads to numerous metabolic disorders such as non-insulin dependent diabetes mellitus. It affects most tissues mainly adipose tissue, liver and muscle. Nowadays, berberine has several medical applications against diseases. The current study was carried out to identify the effect of berberine chloride (BER-chloride) on phosphatidyl inositol-3-kinase/ phosphorylated protein kinase B/ sirtuin type 1/ phosphatase and tension homologue (PI3K/Akt-p/SIRT-1/PTEN) pathway during insulin resistance phenomena. Insulin resistance model was performed in experimental rats by using high fat diet. Plasma glucose, serum insulin, lipid profiles, hepatic oxidative stress markers were estimated. Serum transaminases activities and kidney function tests were determined. Further, hepatic PI3K, AKt-p, SIRT-1; PTEN levels were assayed. The concentration of adiponectin in serum, hepatic tissue and white adipose tissue was determined. Moreover, fold change in hepatic insulin, insulin receptor and retinol binding protein-4 (RBP4) at molecular level was performed. Histopathological study of white adipose tissue was also determined. The results showed increase the rats’ body weights, blood glucose, homeostatic model assessment, glycated hemoglobin, insulin and lipid profiles levels in group of rats fed on high fat diet for eight weeks and this elevation was decreased after administration of BER-chloride for two weeks. Further, BER-chloride administration exhibited improvement of oxidative stress parameters, PI3K, AKt-p, SIRT-1 and PTEN. This was associated with down-regulation of RBP4. According to these data we conclude that, BER-chloride mediated several insulin signaling pathways that could be of therapeutic significance to insulin resistance.

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