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

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 con...

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Main Authors: Ming-Qian He, Jing-Ya Wang, Yue Wang, Jing Sui, Meng Zhang, Xi Ding, Yang Zhao, Zi-Yi Chen, Xiao-Xiao Ren, Bing-Yin Shi
Format: Article
Language:English
Published: Wiley 2020-09-01
Series:Chronic Diseases and Translational Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2095882X20300621
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author Ming-Qian He
Jing-Ya Wang
Yue Wang
Jing Sui
Meng Zhang
Xi Ding
Yang Zhao
Zi-Yi Chen
Xiao-Xiao Ren
Bing-Yin Shi
author_facet Ming-Qian He
Jing-Ya Wang
Yue Wang
Jing Sui
Meng Zhang
Xi Ding
Yang Zhao
Zi-Yi Chen
Xiao-Xiao Ren
Bing-Yin Shi
author_sort Ming-Qian He
collection DOAJ
description 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.
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spelling doaj.art-c6561a7abec84bf8b941ae395943c1032022-12-22T01:19:56ZengWileyChronic Diseases and Translational Medicine2095-882X2020-09-0163198207High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J miceMing-Qian He0Jing-Ya Wang1Yue Wang2Jing Sui3Meng Zhang4Xi Ding5Yang Zhao6Zi-Yi Chen7Xiao-Xiao Ren8Bing-Yin Shi9Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology and International Medical Center, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, China; Corresponding author. Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, China.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.http://www.sciencedirect.com/science/article/pii/S2095882X20300621High-fat dietObesityMetabolic dysfunctionMetabolic inflammation
spellingShingle Ming-Qian He
Jing-Ya Wang
Yue Wang
Jing Sui
Meng Zhang
Xi Ding
Yang Zhao
Zi-Yi Chen
Xiao-Xiao Ren
Bing-Yin Shi
High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
Chronic Diseases and Translational Medicine
High-fat diet
Obesity
Metabolic dysfunction
Metabolic inflammation
title High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
title_full High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
title_fullStr High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
title_full_unstemmed High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
title_short High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL/6J mice
title_sort high fat diet induced adipose tissue expansion occurs prior to insulin resistance in c57bl 6j mice
topic High-fat diet
Obesity
Metabolic dysfunction
Metabolic inflammation
url http://www.sciencedirect.com/science/article/pii/S2095882X20300621
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