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Resveratrol ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via ATM-AMPK axis in skeletal muscle.
Eur Rev Med Pharmacol Sci 2019; 23(20):9117-9125ER

Abstract

OBJECTIVE

Resveratrol (RSV) is a polyphenolic phytoalexin that exhibits diverse pharmacological actions, including its effect on the insulin resistance. However, the mechanism through which RSV improves insulin resistance is not fully understood yet. The aim of this study was to determine the mechanism through which RSV ameliorates insulin resistance in skeletal muscle of high-fat diet (HFD)-induced mouse model, as well as palmitic acid (PA) treated L6 cells, with a specific focus on the response of RSV on fatty acid oxidation.

MATERIALS AND METHODS

Male C57BL6/J mice were randomly divided into three groups: normal diet-fed mice (ND), the high-fat diet-fed mice (HFD), HFD supplemented with RSV (100 mg/kg body weight [BW]/day orally; n = 10). Fasting plasma glucose, insulin, total cholesterol, triglyceride (TG), and free fatty acid levels were determined. The intraperitoneal glucose tolerance test was used to measure blood glucose and area under the curve. The quantitative insulin sensitivity index was calculated to assess insulin resistance. Skeletal muscles were collected for histology study and protein expression measurement. L6 cells were cultured with PA and the glucose concentration in the culture medium, and the intracellular TG levels were tested. RSV, chloroquine, palmitoyltransferase and Ku-55933 were administered to differentiate L6 cells.

RESULTS

The HFD fed mice showed increased BW, hyperglycemia, and hyperlipidemia. The expressions of ataxia telangiectasia mutated (ATM), 5' adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase 1, cytochrome oxidase subunit IV protein were significantly decreased in the skeletal muscles of HFD fed mice and PA-treated L6 cells. All these effects induced by HFD and PA were reversed by RSV treatment.

CONCLUSIONS

ATM is a key factor to improve HFD-induced lipid metabolism and insulin resistance in skeletal muscles. The effects of RSV on ameliorating HFD-induced abnormal lipid metabolism and insulin resistance mediated through ATM-AMPK pathway may due to its improvement in fatty acid oxidation efficiency and sequential reduction in ROS production in skeletal muscle. These results provide important theoretical evidence for the application of RSV in the prevention and treatment of diabetes mellitus and related metabolic diseases.

Authors+Show Affiliations

Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. deshi686300@163.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31696503

Citation

Zhang, Y-J, et al. "Resveratrol Ameliorates High-fat Diet-induced Insulin Resistance and Fatty Acid Oxidation Via ATM-AMPK Axis in Skeletal Muscle." European Review for Medical and Pharmacological Sciences, vol. 23, no. 20, 2019, pp. 9117-9125.
Zhang YJ, Zhao H, Dong L, et al. Resveratrol ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via ATM-AMPK axis in skeletal muscle. Eur Rev Med Pharmacol Sci. 2019;23(20):9117-9125.
Zhang, Y. J., Zhao, H., Dong, L., Zhen, Y. F., Xing, H. Y., Ma, H. J., & Song, G. Y. (2019). Resveratrol ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via ATM-AMPK axis in skeletal muscle. European Review for Medical and Pharmacological Sciences, 23(20), pp. 9117-9125. doi:10.26355/eurrev_201910_19315.
Zhang YJ, et al. Resveratrol Ameliorates High-fat Diet-induced Insulin Resistance and Fatty Acid Oxidation Via ATM-AMPK Axis in Skeletal Muscle. Eur Rev Med Pharmacol Sci. 2019;23(20):9117-9125. PubMed PMID: 31696503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via ATM-AMPK axis in skeletal muscle. AU - Zhang,Y-J, AU - Zhao,H, AU - Dong,L, AU - Zhen,Y-F, AU - Xing,H-Y, AU - Ma,H-J, AU - Song,G-Y, PY - 2019/11/8/entrez PY - 2019/11/7/pubmed PY - 2019/11/7/medline SP - 9117 EP - 9125 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 23 IS - 20 N2 - OBJECTIVE: Resveratrol (RSV) is a polyphenolic phytoalexin that exhibits diverse pharmacological actions, including its effect on the insulin resistance. However, the mechanism through which RSV improves insulin resistance is not fully understood yet. The aim of this study was to determine the mechanism through which RSV ameliorates insulin resistance in skeletal muscle of high-fat diet (HFD)-induced mouse model, as well as palmitic acid (PA) treated L6 cells, with a specific focus on the response of RSV on fatty acid oxidation. MATERIALS AND METHODS: Male C57BL6/J mice were randomly divided into three groups: normal diet-fed mice (ND), the high-fat diet-fed mice (HFD), HFD supplemented with RSV (100 mg/kg body weight [BW]/day orally; n = 10). Fasting plasma glucose, insulin, total cholesterol, triglyceride (TG), and free fatty acid levels were determined. The intraperitoneal glucose tolerance test was used to measure blood glucose and area under the curve. The quantitative insulin sensitivity index was calculated to assess insulin resistance. Skeletal muscles were collected for histology study and protein expression measurement. L6 cells were cultured with PA and the glucose concentration in the culture medium, and the intracellular TG levels were tested. RSV, chloroquine, palmitoyltransferase and Ku-55933 were administered to differentiate L6 cells. RESULTS: The HFD fed mice showed increased BW, hyperglycemia, and hyperlipidemia. The expressions of ataxia telangiectasia mutated (ATM), 5' adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase 1, cytochrome oxidase subunit IV protein were significantly decreased in the skeletal muscles of HFD fed mice and PA-treated L6 cells. All these effects induced by HFD and PA were reversed by RSV treatment. CONCLUSIONS: ATM is a key factor to improve HFD-induced lipid metabolism and insulin resistance in skeletal muscles. The effects of RSV on ameliorating HFD-induced abnormal lipid metabolism and insulin resistance mediated through ATM-AMPK pathway may due to its improvement in fatty acid oxidation efficiency and sequential reduction in ROS production in skeletal muscle. These results provide important theoretical evidence for the application of RSV in the prevention and treatment of diabetes mellitus and related metabolic diseases. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/31696503/Resveratrol_ameliorates_high-fat_diet-induced_insulin_resistance_and_fatty_acid_oxidation_via_ATM-AMPK_axis_in_skeletal_muscle L2 - https://www.europeanreview.org/article/19315 DB - PRIME DP - Unbound Medicine ER -