Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice

Alismatis rhizoma (AR), which is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae), is an important component of many famous Chinese formulas for hypoglycemic. This study aimed to evaluate the insulin resistance (IR) alleviating effects of AR triterpenes (ART) and ART component compatibility (ARTC, the mixture of 16-oxo-alisol A, 16-oxo-alisol A 23-acetate, 16-oxo-alisol A 24-acetate, alisol C, alisol C 23-acetate, alisol L, alisol A, alisol A 23-acetate, alisol A 24-acetate, alisol L 23-acetate, alisol B, alisol B 23-acetate, 11-deoxy-alisol B and 11-deoxy-alisol B 23-acetate) in high-fat diet-induced IR mice and plamitate-treated IR C2C12 cells, respectively. A dose of 200 mg/kg of ART was orally administered to IR mice, and different doses (25, 50, and 100 μg/ml) of ARTC groups were treated to IR C2C12 cells. IPGTT, IPITT, body weight, Hb1AC, FFA, TNF- α , MCP-1, and IR-associated gene expression (p-AMPK, p-IRS-1, PI3K, p-AKT, p-JNK, and GLUT4) were measured in IR mice. Glucose uptake, TNF- α , MCP-1, and IR-associated gene expression were also measured in IR C2C12 cells. Results showed that ART alleviated high-fat diet-induced IR in the skeletal muscle of mice, and this finding was further validated by ARTC. This study demonstrated that ART presented a notable IR alleviating effect by regulating IR-associated gene expression, and triterpenes were the material basis for the IR alleviating activity of AR.

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Combined effect of canagliflozin and exercise training on high-fat diet-fed mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00401.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. E492-E503

Author(s):

Kenichi Tanaka ◽

Hirokazu Takahashi ◽

Sayaka Katagiri ◽

Kazuyo Sasaki ◽

Yujin Ohsugi ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Exercise Training ◽

Fatty Liver ◽

High Fat Diet ◽

Characteristic Change ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Sodium Glucose Cotransporter

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been reported to improve obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) in addition to exercise training, whereas the combined effects remain to be elucidated fully. We investigated the effect of the combination of the SGLT2i canagliflozin (CAN) and exercise training in high-fat diet-induced obese mice. High-fat diet-fed mice were housed in normal cages (sedentary; Sed) or wheel cages (WCR) with or without CAN (0.03% of diet) for 4 wk. The effects on obesity, glucose metabolism, and hepatic steatosis were evaluated in four groups (Control/Sed, Control/WCR, CAN/Sed, and CAN/WCR). Numerically additive improvements were found in body weight, body fat mass, blood glucose, glucose intolerance, insulin resistance, and the fatty liver of the CAN/WCR group, whereas CAN increased food intake and reduced running distance. Exercise training alone, CAN alone, or both did not change the weight of skeletal muscle, but microarray analysis showed that each resulted in a characteristic change of gene expression in gastrocnemius muscle. In particular, in the CAN/WCR group, there was acceleration of the angiogenesis pathway and suppression of the adipogenesis pathway compared with the CAN/Sed group. In conclusion, the combination of an SGLT2i and exercise training improves obesity, insulin resistance, and NAFLD in an additive manner. Changes of gene expression in skeletal muscle may contribute, at least in part, to the improvement of obesity and insulin sensitivity.

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Lack of skeletal muscle liver kinase B1 alters gene expression, mitochondrial content, inflammation and oxidative stress without affecting high-fat diet-induced obesity or insulin resistance

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2020.165805 ◽

2020 ◽

Vol 1866 (8) ◽

pp. 165805 ◽

Cited By ~ 1

Author(s):

Ting Chen ◽

Jonathon T. Hill ◽

Timothy M. Moore ◽

Eric C.K. Cheung ◽

Zachary E. Olsen ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

High Fat Diet ◽

High Fat ◽

Mitochondrial Content ◽

Diet Induced Obesity ◽

Liver Kinase B1 ◽

And Oxidative Stress

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Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice

Frontiers in Physiology ◽

10.3389/fphys.2021.676265 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alice C. Rodrigues ◽

Alexandre R. Spagnol ◽

Flávia de Toledo Frias ◽

Mariana de Mendonça ◽

Hygor N. Araújo ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Oxygen Consumption ◽

Insulin Sensitivity ◽

Mitochondrial Respiration ◽

High Fat Diet ◽

C2c12 Cells ◽

High Fat ◽

Spare Capacity

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

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Effects of Exercise Intensity on PGC-1α, PPAR-γ, and Insulin Resistance in Skeletal Muscle of High Fat Diet-fed Sprague-Dawley Rats

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2014.43.7.963 ◽

2014 ◽

Vol 43 (7) ◽

pp. 963-971

Author(s):

Hyun-Lyung Jung ◽

Ho-Youl Kang

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Exercise Intensity ◽

High Fat Diet ◽

Sprague Dawley ◽

High Fat ◽

Ppar Γ ◽

Sprague Dawley Rats

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Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

British Journal of Pharmacology ◽

10.1111/bph.14802 ◽

2019 ◽

Vol 176 (20) ◽

pp. 3983-4001 ◽

Cited By ~ 8

Author(s):

Shengnan Shen ◽

Qiwen Liao ◽

Tian Zhang ◽

Ruile Pan ◽

Ligen Lin

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity

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Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽

10.1161/circ.118.suppl_18.s_1169-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Rieko Takanabe ◽

Koh Ono ◽

Tomohide Takaya ◽

Takahiro Horie ◽

Hiromichi Wada ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

High Fat Diet ◽

Control Cell ◽

High Fat ◽

Expression Levels ◽

Mesenteric Fat ◽

Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

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