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Exp Clin Endocrinol Diabetes 2023; 131(11): 595-604
DOI: 10.1055/a-2178-9113
Article

Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice

Piaojian Yu
1   Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
3   Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University
,
Wei Wang
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
4   Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
,
Wanrong Guo
1   Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
,
Lidan Cheng
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
4   Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
,
Zhiping Wan
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
5   Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
,
Yanglei Cheng
7   Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
,
Yunfeng Shen
4   Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
6   Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, Jiangxi Province, China
,
Fen Xu
1   Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China
3   Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University
› Author Affiliations Funding Information Guangzhou Municipal Science and Technology Project — 202102010229 Local Innovative and Research Teams Projects of Guangdong Pearl River Talents Program — 2017BT01S131 National Natural Science Foundation of China Grant — 81970741, 82270942
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Abstract

Introduction Pioglitazone is an insulin sensitizer used for the treatment of type 2 diabetes mellitus (T2DM) by activating peroxisome proliferator-activated receptor gamma. This study aimed to investigate the effects of pioglitazone on white adipose tissue (WAT) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice.

Methods C57BL/6 mice were treated with pioglitazone (30 mg/kg/day) for 4 weeks after a 16-week high-fat diet (HFD) challenge. Body weight gain, body fat mass, energy intake, and glucose homeostasis were measured during or after the treatment. Histopathology was observed by hematoxylin and eosin, oil red O, immunohistochemistry, and immunofluorescence staining. Expression of thermogenic and mitochondrial biogenesis-related genes was detected by quantitative real-time PCR and western blotting.

Results After 4-week pioglitazone treatment, the fasting blood glucose levels, glucose tolerance, and insulin sensitivity were significantly improved, but the body weight gain and fat mass were increased in DIO mice. Compared with the HFD group, pioglitazone did not significantly affect the weights of liver and WAT in both subcutaneous and epididymal regions. Unexpectedly, the weight of BAT was increased after pioglitazone treatment. Histological staining revealed that pioglitazone ameliorated hepatic steatosis, reduced the adipocyte size in WAT, but increased the adipocyte size in BAT.

Conclusion Though pioglitazone can promote lipolysis, thermogenesis, and mitochondrial function in WAT, it leads to impaired thermogenesis, and mitochondrial dysfunction in BAT. In conclusion, pioglitazone could promote the browning of WAT but led to the whitening of BAT; the latter might be a new potential mechanism of pioglitazone-induced weight gain during T2DM treatment.

Key words

pioglitazone - brown fat - whitening - weight gain - T2DM

Supplementary Material



Publication History

Received: 13 June 2023
Received: 19 September 2023

Accepted: 10 August 2023
Accepted: 20 September 2023

Accepted Manuscript online:
20 September 2023

Article published online:
03 November 2023

© 2023. Thieme. All rights reserved.

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