Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway

Zhao, Xiaona; Shen, Cheng; Zhu, Hong; Wang, Cong; Liu, Xiangwei; Sun, Xiaolei; Han, Shasha; Wang, Peng; Dong, Zhen; Ma, Xin; Hu, Kai; Sun, Aijun; Ge, Junbo

doi:10.3390/molecules21060705

Volume 21, Issue 6

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Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway

Xiaona Zhao^1,†, Cheng Shen^1,†, Hong Zhu¹, Cong Wang¹, Xiangwei Liu¹, Xiaolei Sun^1,2, Shasha Han¹, Peng Wang¹, Zhen Dong¹, Xin Ma^1,2, Kai Hu¹, Aijun Sun^1,2,* and Junbo Ge^1,2,*

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China

Institute of Biomedical Science, Fudan University, Shanghai 200032, China

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editors: Min-Hsiung Pan and Filomena Conforti

Molecules 2016, 21(6), 705; https://doi.org/10.3390/molecules21060705

Received: 23 March 2016 / Revised: 12 May 2016 / Accepted: 19 May 2016 / Published: 30 May 2016

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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Abstract

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway. View Full-Text

Keywords: trans-fatty acid; obesity; insulin resistance; hepatic steatosis

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Zhao, X.; Shen, C.; Zhu, H.; Wang, C.; Liu, X.; Sun, X.; Han, S.; Wang, P.; Dong, Z.; Ma, X.; Hu, K.; Sun, A.; Ge, J. Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway. Molecules 2016, 21, 705.