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[Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism].
Zhonghua Yi Xue Za Zhi 2017; 97(2):131-136ZY

Abstract

Objective:

To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice.

Methods:

Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg-1·d-1 exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group. Additional 6 mice were also selected as control group. Body weight, fasting blood glucose were recorded. Serum triglyceride (TG), total cholesterol (TC), insulin and skeletal muscle triglyceride levels were measured by enzyme-linked immunosobent assay (ELISA). Oil red O staining was used for morphologic changes of frozen sections from skeletal muscle. The protein levels of lipid metabolic pathway mediated by AMP-activated protein kinase (AMPK) and insulin signailing pathway were determined by Western blot.

Results:

Compared with mice in HFD group, exendin-4 significantly decreased body weight[(37.68±1.80) vs (46.03±5.00) g, P<0.025], fasting blood glucose[(5.40±0.33) vs (7.65±1.92) mmol/L, P<0.025], serum TG[(37.78±7.14) vs (80.76±34.22) mg/dl, P<0.025], TC[(180.13±18.75) vs (217.57±22.52) mg/dl, P<0.025], insulin[(0.58±0.01) vs (1.67±1.23) ng/ml, P<0.025]and skeletal muscle TG levels[(9.84±1.08) vs (19.35±7.44) mg/g, P<0.025]of obese mice. Oil red O staining revealed that exendin-4 alleviated the accumulation of larger lipid droplets in skeletal muscle. The protein expressions of lipolysis and lipid oxidation mediated by AMPK and insulin signailing pathway were up-regulated, and the protein expressions of lipogenesis mediated by AMPK were down-regulated after intervention of exendin-4.

Conclusion:

Exendin-4 reduces lipid deposition and insulin resistance in skeletal muscle of HFD-induced obese mice via activating AMPK and up-regulating insulin signailing pathway.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Third Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou 510630, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

chi

PubMed ID

28088959

Citation

Cao, H Y., et al. "[Effect of Exendin-4 On Lipid Deposition in Skeletal Muscle of Diet-induced Obese Mice and Its Underlying Mechanism]." Zhonghua Yi Xue Za Zhi, vol. 97, no. 2, 2017, pp. 131-136.
Cao HY, Xu F, Chen ZL, et al. [Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism]. Zhonghua Yi Xue Za Zhi. 2017;97(2):131-136.
Cao, H. Y., Xu, F., Chen, Z. L., Lin, B. S., Zheng, X. B., Yuan, S. H., ... Weng, J. P. (2017). [Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism]. Zhonghua Yi Xue Za Zhi, 97(2), pp. 131-136. doi:10.3760/cma.j.issn.0376-2491.2017.02.011.
Cao HY, et al. [Effect of Exendin-4 On Lipid Deposition in Skeletal Muscle of Diet-induced Obese Mice and Its Underlying Mechanism]. Zhonghua Yi Xue Za Zhi. 2017 Jan 10;97(2):131-136. PubMed PMID: 28088959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism]. AU - Cao,H Y, AU - Xu,F, AU - Chen,Z L, AU - Lin,B S, AU - Zheng,X B, AU - Yuan,S H, AU - Liang,H, AU - Weng,J P, PY - 2017/1/17/entrez PY - 2017/1/17/pubmed PY - 2018/8/22/medline SP - 131 EP - 136 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 97 IS - 2 N2 - Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg-1·d-1 exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group. Additional 6 mice were also selected as control group. Body weight, fasting blood glucose were recorded. Serum triglyceride (TG), total cholesterol (TC), insulin and skeletal muscle triglyceride levels were measured by enzyme-linked immunosobent assay (ELISA). Oil red O staining was used for morphologic changes of frozen sections from skeletal muscle. The protein levels of lipid metabolic pathway mediated by AMP-activated protein kinase (AMPK) and insulin signailing pathway were determined by Western blot. Results: Compared with mice in HFD group, exendin-4 significantly decreased body weight[(37.68±1.80) vs (46.03±5.00) g, P<0.025], fasting blood glucose[(5.40±0.33) vs (7.65±1.92) mmol/L, P<0.025], serum TG[(37.78±7.14) vs (80.76±34.22) mg/dl, P<0.025], TC[(180.13±18.75) vs (217.57±22.52) mg/dl, P<0.025], insulin[(0.58±0.01) vs (1.67±1.23) ng/ml, P<0.025]and skeletal muscle TG levels[(9.84±1.08) vs (19.35±7.44) mg/g, P<0.025]of obese mice. Oil red O staining revealed that exendin-4 alleviated the accumulation of larger lipid droplets in skeletal muscle. The protein expressions of lipolysis and lipid oxidation mediated by AMPK and insulin signailing pathway were up-regulated, and the protein expressions of lipogenesis mediated by AMPK were down-regulated after intervention of exendin-4. Conclusion: Exendin-4 reduces lipid deposition and insulin resistance in skeletal muscle of HFD-induced obese mice via activating AMPK and up-regulating insulin signailing pathway. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/28088959/[Effect_of_exendin_4_on_lipid_deposition_in_skeletal_muscle_of_diet_induced_obese_mice_and_its_underlying_mechanism]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2017&amp;vol=97&amp;issue=2&amp;fpage=131 DB - PRIME DP - Unbound Medicine ER -