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

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 ener...

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Published in:Molecular metabolism (Germany) 2021-05, Vol.47, p.101182-101182, Article 101182
Main Authors: Huang, Meiqin, Lin, Yijun, Wang, Lin, You, Xue, Wang, Shuo, Zhao, Jingyu, Bai, Meijuan, Li, Zixuan, Chen, Yan
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container_title Molecular metabolism (Germany)
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description 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. •Paqr11 deletion promotes lipolysis in epididymal white adipose tissue.•PAQR11 modulates cAMP level by altering protein degradation of PDE4D.•PAQR11 affects the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex.•PAQR11 regulates starvation-induced lipolysis in adipose tissue.
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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. •Paqr11 deletion promotes lipolysis in epididymal white adipose tissue.•PAQR11 modulates cAMP level by altering protein degradation of PDE4D.•PAQR11 affects the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex.•PAQR11 regulates starvation-induced lipolysis in adipose tissue.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>33549845</pmid><doi>10.1016/j.molmet.2021.101182</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Adipocytes - metabolism
Adipose Tissue - metabolism
Adipose Tissue, White - metabolism
Animals
cAMP
Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism
Diet, High-Fat - adverse effects
Energy Metabolism
Fatty Acids, Nonesterified - metabolism
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Lipase - metabolism
Lipid Metabolism
Lipolysis
Lipolysis - physiology
Male
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Obesity
Obesity - metabolism
Original
PDE4D
Perilipin-1 - metabolism
PKA
Protein Stability
Sterol Esterase - metabolism
Transcriptome
Triglycerides - metabolism
Ubiquitination
title Adipose tissue lipolysis is regulated by PAQR11 via altering protein stability of phosphodiesterase 4D
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