Medium-chain triglyceride ameliorates insulin resistance and inflammation 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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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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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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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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Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

International Journal of Obesity ◽

10.1038/s41366-020-00657-6 ◽

2020 ◽

Vol 44 (11) ◽

pp. 2323-2334

Author(s):

Belén Chanclón ◽

Yanling Wu ◽

Milica Vujičić ◽

Marco Bauzá-Thorbrügge ◽

Elin Banke ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Insulin Levels ◽

Fat Depots ◽

Fat Depot

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

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Synergistic effect of sea cucumber saponins and EPA-enriched phospholipids on insulin resistance in high-fat diet-induced obese mice

Food & Function ◽

10.1039/c9fo01147a ◽

2019 ◽

Vol 10 (7) ◽

pp. 3955-3964 ◽

Cited By ~ 3

Author(s):

Xiu-Qing Han ◽

Ling-Yu Zhang ◽

Lin Ding ◽

Hao-Hao Shi ◽

Chang-Hu Xue ◽

...

Keyword(s):

Insulin Resistance ◽

Synergistic Effect ◽

High Fat Diet ◽

Sea Cucumber ◽

Insulin Response ◽

Obese Mice ◽

High Fat

The combination of sea cucumber saponins (SCS) and EPA-PL contributed to a synergistic effect on alleviating the obesity-related insulin resistance due to the amelioration of an inflammation centric peripheral insulin response.

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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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Addendum: de Souza Mesquita, L.M., et al. Modulatory Effect of Polyphenolic Compounds from the Mangrove Tree Rhizophora mangle L. on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in High-Fat Diet Obese Mice. Molecules, 2018, 23, 2114

Molecules ◽

10.3390/molecules24010169 ◽

2019 ◽

Vol 24 (1) ◽

pp. 169

Author(s):

Leonardo Mendes De Souza Mesquita ◽

Cíntia Rabelo e Paiva Caria ◽

Paola Souza Santos ◽

Caio Cesar Ruy ◽

Natalia Da Silva Lima ◽

...

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Polyphenolic Compounds ◽

Obese Mice ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Mangrove Tree ◽

Alcoholic Fatty Liver Disease

The authors wish to add the process number in the Acknowledgments section in this paper [...]

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The Fruit of Acanthopanax Senticosus (Rupr. Et Maxim) Harms, or Goka, Improves Insulin Resistance in High-Fat Diet Fed Obese Mice

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2016.10.469 ◽

2016 ◽

Vol 100 ◽

pp. S177

Author(s):

Tetsuo Saito ◽

Miyako Nishida ◽

Masafumi Saito ◽

Takahiro Eitsuka ◽

Hiroshi Nishida

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Acanthopanax Senticosus

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Double-Stranded RNA-Activated Protein Kinase Is a Key Modulator of Insulin Sensitivity in Physiological Conditions and in Obesity in Mice

Endocrinology ◽

10.1210/en.2012-1400 ◽

2012 ◽

Vol 153 (11) ◽

pp. 5261-5274 ◽

Cited By ~ 43

Author(s):

M. A. Carvalho-Filho ◽

B. M. Carvalho ◽

A. G. Oliveira ◽

D. Guadagnini ◽

M. Ueno ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Protein Phosphatase ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Double Stranded Rna ◽

Physiological Conditions ◽

Phosphatase 2A

Abstract The molecular integration of nutrient- and pathogen-sensing pathways has become of great interest in understanding the mechanisms of insulin resistance in obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate molecule that may provide cross talk between inflammatory and metabolic signaling. The present study was performed to determine, first, the role of PKR in modulating insulin action and glucose metabolism in physiological situations, and second, the role of PKR in insulin resistance in obese mice. We used Pkr−/− and Pkr+/+ mice to investigate the role of PKR in modulating insulin sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and adipose tissue in response to a high-fat diet. Our data show that in lean Pkr−/− mice, there is an improvement in insulin sensitivity, and in glucose tolerance, and a reduction in fasting blood glucose, probably related to a decrease in protein phosphatase 2A activity and a parallel increase in insulin-induced thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of obese mice and can induce insulin resistance by directly binding to and inducing insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly through modulation of c-Jun N-terminal kinase and inhibitor of κB kinase β. Pkr−/− mice were protected from high-fat diet-induced insulin resistance and glucose intolerance and showed improved insulin signaling associated with a reduction in c-Jun N-terminal kinase and inhibitor of κB kinase β phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin sensitivity under normal physiological conditions, probably by modulating protein phosphatase 2A activity and serine-threonine kinase phosphorylation, and certainly, this kinase may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity.

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