High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice

Chronic Diseases and Translational Medicine

Jing Sui¹  Yang Zhao²  Xiao-Xiao Ren²  Meng Zhang²  Ming-Qian He²  Xi Ding²  Jing-Ya Wang²  Zi-Yi Chen²  Yue Wang²  Bing-Yin Shi² 

[1] Department of Endocrinology and International Medical Center, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China;Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China;

关键词: High-fat diet;    Obesity;    Metabolic dysfunction;    Metabolic inflammation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: To date, there is only scare evidence characterizing the temporal features and progression of metabolic dysfunction in high-fat diet (HFD)-fed obese mice. Hence, its specific pathogenesis remains unclear. Methods: Sixty 6-week-old male C57BL/6J mice were randomly divided into HFD and control diet (CD) groups and sacrificed at 1, 5, 9, 13, 17, and 21 weeks, respectively. At weekly intervals, intraperitoneal glucose tolerance testing (IPGTT) and intraperitoneal insulin tolerance testing (IPITT) were performed in both groups. A detailed time course in HFD-fed mice was investigated by evaluating the initiation of glucose homeostasis impairment, dyslipidemia, systemic insulin sensitivity, monocyte chemoattractant protein-1 (MCP-1) levels, epididymal white adipose tissue (eWAT) expansion, macrophage content changes, pro-inflammatory (M1)/anti-inflammatory (M2) macrophage imbalance, lipid accumulation in the liver, and β-cell morphometry in the pancreas. Results: In the HFD group, progressive weight gain and impairments in glucose metabolism (elevated fasting blood glucose and area under the curve (AUC) of IPGTT) were observed from the 3rd week, and a significantly elevated AUC of IPITT was first detected after week 7 of HFD feeding. As for dyslipidemia, after 9 weeks of feeding, the low-density lipoprotein cholesterol level and total cholesterol level in HFD group were significantly higher than those in the CD group (all P < 0.05), whereas no significant differences were shown in triglyceride level. Adipocyte size increased significantly in the HFD group in the 1st week, a phenotypic switch in eWAT from anti-inflammatory (M2) to pro-inflammatory (M1) macrophages was observed in the 5th week, and the metabolic inflammation was distinct in eWAT in the 9th week. Additionally, liver steatosis was considerably obvious at the 17th week and pancreatic β-cell morphometry did not change during 21 weeks of HFD feeding. Conclusion: The eWAT expansion was detected early in HFD-induced obese mice, which occurred prior to obvious insulin resistance.

【 授权许可】

Unknown