PMID- 32885155 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220416 IS - 2589-0514 (Electronic) IS - 2095-882X (Print) IS - 2095-882X (Linking) VI - 6 IP - 3 DP - 2020 Sep TI - High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice. PG - 198-207 LID - 10.1016/j.cdtm.2020.06.003 [doi] AB - 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 beta-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 beta-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. CI - (c) 2020 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. FAU - He, Ming-Qian AU - He MQ AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Wang, Jing-Ya AU - Wang JY AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Wang, Yue AU - Wang Y AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Sui, Jing AU - Sui J AD - Department of Endocrinology and International Medical Center, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Zhang, Meng AU - Zhang M AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Ding, Xi AU - Ding X AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Zhao, Yang AU - Zhao Y AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Chen, Zi-Yi AU - Chen ZY AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Ren, Xiao-Xiao AU - Ren XX AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. FAU - Shi, Bing-Yin AU - Shi BY AD - Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China. LA - eng PT - Journal Article DEP - 20200718 PL - United States TA - Chronic Dis Transl Med JT - Chronic diseases and translational medicine JID - 101679934 PMC - PMC7451745 OTO - NOTNLM OT - High-fat diet OT - Metabolic dysfunction OT - Metabolic inflammation OT - Obesity COIS- None. EDAT- 2020/09/05 06:00 MHDA- 2020/09/05 06:01 PMCR- 2020/07/18 CRDT- 2020/09/05 06:00 PHST- 2019/11/09 00:00 [received] PHST- 2020/09/05 06:00 [entrez] PHST- 2020/09/05 06:00 [pubmed] PHST- 2020/09/05 06:01 [medline] PHST- 2020/07/18 00:00 [pmc-release] AID - S2095-882X(20)30062-1 [pii] AID - 10.1016/j.cdtm.2020.06.003 [doi] PST - epublish SO - Chronic Dis Transl Med. 2020 Jul 18;6(3):198-207. doi: 10.1016/j.cdtm.2020.06.003. eCollection 2020 Sep.