Mulberry ( Morus alba L.) leaf polysaccharide ameliorates insulin resistance‐ and adipose deposition‐associated gut microbiota and lipid metabolites in high‐fat diet‐induced obese mice

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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Hydroxytyrosol Improves Obesity and Insulin Resistance by Modulating Gut Microbiota in High-Fat Diet-Induced Obese Mice

Frontiers in Microbiology ◽

10.3389/fmicb.2019.00390 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 12

Author(s):

Zhuoqun Liu ◽

Ningning Wang ◽

Yanan Ma ◽

Deliang Wen

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

High Fat Diet ◽

Obese Mice ◽

High Fat

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Bifidobacterium animalis subsp. lactis lkm512 attenuates obesity‐associated inflammation and insulin resistance through the modification of gut microbiota in high‐fat diet‐induced obese mice

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202100639 ◽

2021 ◽

pp. 2100639

Author(s):

Lingyan Ma ◽

Aqian Zheng ◽

Liyang Ni ◽

Lianxin Wu ◽

Luting Hu ◽

...

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Bifidobacterium Animalis

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Dietary Momordica Cochinchinensis aril ameliorates metabolic dysfunction, nonalcoholic fatty liver, and gut microbiota in diet-induced obese mice

10.21203/rs.2.20237/v1 ◽

2020 ◽

Author(s):

Yu-Chun Lin ◽

Hsiu-Chen Huang ◽

Yu-Heng Lai ◽

Jui-Chieh Chen ◽

Hsiao-Hsuan Tien ◽

...

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Fatty Liver ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Metabolic Dysfunction ◽

Obese Mice ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Momordica Cochinchinensis

Abstract Background Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis fruit is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic dysfunction and gut microbiota remains unclear. This study was conducted to determine how Momordica cochinchinensis aril (MCA) affects obesity, nonalcoholic fatty liver, insulin resistance and gut microbiota in diet-induced obese mice.Methods Wild type male mice at age of 5 weeks received four different kinds of diets: a normal diet, high-fat diet (HFD), or HFD supplemented with 1% or 3% (wt:wt) lyophilized MCA for 10 weeks. Body weight, adipose tissue and liver weight, serum biochemical parameters, glucose tolerance and liver lipids were measured. Gut microbial composition was analyzed.Results MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver inflammation were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of AMPK and PPAR-alpha signaling pathway in the human fatty liver HuS-E/2 cell model. Supplementation with MCA resulted in microbiota populations changed significantly.Conclusion Our data indicate that dietary MCA is involved in the prevention of HFD-induced adiposity, insulin resistance and nonalcoholic fatty liver disease and altered the microbial contents of the gut and modulated microbial dysbiosis in the host.

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CaMKIV limits metabolic damage through induction of hepatic autophagy by CREB in obese mice

Journal of Endocrinology ◽

10.1530/joe-19-0251 ◽

2020 ◽

Vol 244 (2) ◽

pp. 353-367 ◽

Cited By ~ 2

Author(s):

Jiali Liu ◽

Yue Li ◽

Xiaoyan Zhou ◽

Xi Zhang ◽

Hao Meng ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Inflammatory Response ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Insulin Action ◽

Hepatic Insulin Resistance ◽

Obese Mice ◽

High Fat ◽

Impaired Insulin

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

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Lactobacillus rhamnosus strain LRH05 intervention ameliorated body weight gain and adipose inflammation via modulating the gut microbiota in high‐fat diet‐induced obese mice

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202100348 ◽

2021 ◽

pp. 2100348

Author(s):

Yung‐Tsung Chen ◽

Shiou‐Yun Chiou ◽

Ai‐Hua Hsu ◽

Yu‐Chun Lin ◽

Jin‐Seng Lin

Keyword(s):

Body Weight ◽

Weight Gain ◽

Gut Microbiota ◽

High Fat Diet ◽

Body Weight Gain ◽

Lactobacillus Rhamnosus ◽

Obese Mice ◽

High Fat ◽

Adipose Inflammation

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Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000783 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000783 ◽

Cited By ~ 7

Author(s):

Liang Xu ◽

Naoto Nagata ◽

Guanliang Chen ◽

Mayumi Nagashimada ◽

Fen Zhuge ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Energy Expenditure ◽

Chronic Inflammation ◽

Plasma Levels ◽

High Fat Diet ◽

Macrophage Activation ◽

Low Grade ◽

Obese Mice ◽

High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

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Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice

Molecules ◽

10.3390/molecules25174001 ◽

2020 ◽

Vol 25 (17) ◽

pp. 4001

Author(s):

Sen Guo ◽

Haoan Zhao ◽

Zhongxiao Ma ◽

Shanshan Zhang ◽

Mingrou Li ◽

...

Keyword(s):

Gut Microbiota ◽

Pancreatic Lipase ◽

Inhibitory Activity ◽

High Fat Diet ◽

Obese Mice ◽

Modulation Effect ◽

Fraxinus Mandshurica ◽

High Fat ◽

Stress Injury ◽

Phytochemical Study

Previously we conducted a phytochemical study on the seeds of Fraxinus excelsior and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of Fraxinus mandshurica seeds have not been studied. In the present study, we investigated the secoiridoid compounds in F. mandshurica seed extract (FM) using column chromatography, 1H-NMR, 13C-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect of FM on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from FM and identified. The total content of secoiridoids in FM reached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 μM. After obese mice were administrated with FM at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, FM could attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice. FM could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes, Bacteroidia, S24-7 and Allobaculum), and reducing the proportion of obesogenic gut microbiota (Firmicutes and Dorea). This study suggests that F. mandshurica seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.

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Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

AJP Cell Physiology ◽

10.1152/ajpcell.00064.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1172-C1182 ◽

Cited By ~ 3

Author(s):

Min-Gyeong Shin ◽

Hye-Na Cha ◽

Soyoung Park ◽

Yong-Woon Kim ◽

Jong-Yeon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

High Fat Diet ◽

Control Diet ◽

In Vivo Studies ◽

Selenoprotein W ◽

Obese Mice ◽

High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

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