Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16
Year: 2019
Type: article
Abstract: Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.
Source: Cell Reports
Authors: Yusuke Nakatsu, Yasuka Matsunaga, Takeshi Yamamotoya, Koji Ueda, Masa-ki Inoue, Yu Mizuno, Mikako Nakanishi, Tomomi Sano, Yosuke Yamawaki, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Akihide Ryo, Hiraku Ono, Tohru Minamino, Shin-Ichiro Takahashi, Haruya Ohno, Masayasu Yoneda, Kei Takahashi, Hisamitsu Ishihara, Hideki Katagiri, Fusanori Nishimura, Takashi Kanematsu, Tetsuya Yamada, Tomoichiro Asano
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Study on PRIP roles in cancer cell proliferation and migration, Development of a new treatment for obese diabetic periodontitis using anti-inflammatory miRNA-encapsulating exosomes, Direct and Indirect Effects of Insulin on Target Tissues to Decrease Glucose, G3008764365, Elucidation of vagal mechanism underlying glucose homeostasis, Antitumor drug development research focusing on the novel cancer cell regulation mechanism of PRIP, Hepatic insulin action affects energy expenditure, Related elucidation of the tissue-specific pudding metabolism state and lifestyle-related disease, Research for elucidating mechanisms of stress vulnerability as basis of brain dysfunction caused by periodontal disease, Prolyl isomerase Pin1 suppresses thermogenesis, Significance of Trk-fused gene (TFG) in the pathogenesis of obesity and metabolic disorders, Mechanisms of brown fat differentiation through chromatin modification, Development of methods to regulate abnormality of insulin-like activity by modulation of function of insulin receptor substrates-associated complex, Roles of Pin1 and PAR 14 on the metabolic regulations
OpenAlex ID: W2924809398