title: Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.
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&amp;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.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. zhaoxiaona1224@sina.cn.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. shencheng1117@126.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. zhuhongisme@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. 13211210017@fudan.edu.cn.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. Liuxiangwei1224@126.com.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. 18516089416@sina.cn.|Institute of Biomedical Science, Fudan University, Shanghai 200032, China. 18516089416@sina.cn.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. zxc1990217@sina.com.
authors.forename: Shasha
authors.initials: S
authors.lastname: Han
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. 18463739133@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. Fionazhao123@aliyun.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. Moveforward2013@yean.net.|Institute of Biomedical Science, Fudan University, Shanghai 200032, China. Moveforward2013@yean.net.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. hu.kai@zs-hospital.sh.cn.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. sun.aijun@zs-hospital.sh.cn.|Institute of Biomedical Science, Fudan University, Shanghai 200032, China. sun.aijun@zs-hospital.sh.cn.
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. jbge@zs-hospital.sh.cn.|Institute of Biomedical Science, Fudan University, Shanghai 200032, China. jbge@zs-hospital.sh.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D050171:Dyslipidemias / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D015398:Signal Transduction; D044242:Trans Fatty Acids / Q000378:metabolism*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008055:Lipids; D044242:Trans Fatty Acids
keywords: hepatic steatosis; insulin resistance; obesity; trans-fatty acid