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https://ir.cnu.edu.tw/handle/310902800/34565
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標題: | Augmented CCL5/CCR5 signaling in brown adipose tissue inhibits adaptive thermogenesis and worsens insulin resistance in |
作者: | Chan, Pei-Chi Hung, Li-Man Huang, Jiung-Pang Day, Yuan-Ji Yu, Chao-Lan Kuo, Feng-Chih Lu, Chieh-Hua Tian, Yu-Feng Hsieh, Po-Shiuan |
貢獻者: | National Defense Medical Center Chang Gung University Chang Gung University Tri-Service General Hospital Chi Mei Hospital Chia Nan University of Pharmacy & Science Tri-Service General Hospital |
關鍵字: | activated protein-kinase macrophage recruitment cold-exposure fat metabolism adipocyte obesity beige lipolysis ampk |
日期: | 2022 |
上傳時間: | 2023-12-11 13:58:10 (UTC+8) |
出版者: | PORTLAND PRESS LTD |
摘要: | Chemokine (C-C motif) ligand 5 (CCL5) and CCR5, one of its receptors have been reported to be highly expressed in white adipose tissue (WAT) and are associated with the progression of inflammation and the development of insulin resistance in obese humans and mice. However, the role of CCL5/CCR5 signaling in obesity-associated dysregulation of energy metabolism remains unclear. Here, we demonstrate that global CCL5/CCR5 double knockout (DKO) mice have higher cold stress-induced energy expenditure and thermogenic function in brown adipose tissue (BAT) than wildtype (WT) mice. DKO mice have higher cold stress-induced energy expenditure and thermogenic function in BAT than WT mice. KEGG pathway analysis indicated that deletion of CCL5/CCR5 further facilitated the cold-induced expression of genes related to oxidative phosphorylation (OxPhos) and lipid metabolic pathways. In primary brown adipocytes of DKO mice, the augmentation of CL-316243-stimulated thermogenic and lipolysis responses was reversed by co-treatment with AMPK alpha 1 and alpha 2 short interfering RNA (siRNA). Overexpression of BAT CCL5/CCR5 genes by local lentivirus injection in WT mice suppressed cold stress-induced lipolytic processes and thermogenic activities. In contrast, knockdown of BAT CCL5/CCR5 signaling further up-regulated AMPK phosphorylation as well as thermogenic and lipolysis responses to chronic adrenergic stimuli and subsequently decreased level of body weight gain. Chronic knockdown of BAT CCL5/CCR5 signaling improved high-fat diet (HFD)-induced insulin resistance in WT mice. It is suggested that obesity-induced augmentation of adipose tissue (AT) CCL5/CCR5 signaling could, at least in part, suppress energy expenditure and adaptive thermogenesis by inhibiting AMPK-mediated lipolysis and oxidative metabolism in thermogenic AT to exacerbate the development of obesity and insulin resistance. |
關聯: | CLINICAL SCIENCE, v.136, n.1, pp.121–137 |
顯示於類別: | [保健營養系(所) ] 期刊論文
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