Adipose tissue lipolysis is regulated by PAQR11 via altering protein stability of phosphodiesterase 4D

Meiqin Huang; Yijun Lin; Lin Wang; Xue You; Shuo Wang; Jingyu Zhao; Meijuan Bai; Zixuan Li; Yan Chen

Molecular Metabolism (May 2021)

Adipose tissue lipolysis is regulated by PAQR11 via altering protein stability of phosphodiesterase 4D

Meiqin Huang,
Yijun Lin,
Lin Wang,
Xue You,
Shuo Wang,
Jingyu Zhao,
Meijuan Bai,
Zixuan Li,
Yan Chen

Affiliations

Meiqin Huang: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yijun Lin: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Lin Wang: China Animal Health and Epidemiology Center, Qingdao, Shangdong, 266032, China
Xue You: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Shuo Wang: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Jingyu Zhao: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Meijuan Bai: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Zixuan Li: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yan Chen: CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Corresponding author.

Journal volume & issue: Vol. 47
p. 101182

Abstract

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Fat storage and mobilization in adipose tissue play a central role in energy metabolism and are directly linked to the development of obesity. Upon starvation, fat is mobilized from adipose tissue by lipolysis, a process by which triglycerides are hydrolyzed to free fatty acids to be used as an energy source in skeletal muscles and other tissues. However, how lipolysis is activated by starvation is not fully known. In this study, we demonstrate that PAQR11, a member of the progesterone and AdipoQ receptor family, regulates starvation-mediated lipolysis. Paqr11-deleted mice are resistant to high-fat diet-induced obesity. Paqr11 deletion promotes lipolysis in white adipose tissue, characterized by increased phosphorylations of hormone-sensitive lipase (HSL) and perilipin 1 (PLIN1) and elevated serum levels of glycerol and free fatty acids. PKA activity and cAMP levels in white adipose tissue are also increased by Paqr11 deletion, accompanied by accelerated protein degradation of phosphodiesterase 4D (PDE4D). Mechanistically, PAQR11 decreases the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex, thus modulating the polyubiquitination/degradation of PDE4D. Fasting decreases the expression of the Paqr11 gene, and starvation-induced lipolysis in white adipose tissue is enhanced by Paqr11 deletion, while insulin-mediated suppression of lipolysis is not affected. Collectively, these results reveal that PAQR11 regulates lipolysis of adipose tissue and affects high-fat diet-induced obesity.

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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