Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.
Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity.
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Lei
L
Ding
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Feng
F
Zhang
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Ming-Xia
MX
Zhao
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Xing-Sheng
XS
Ren
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Qi
Q
Chen
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Yue-Hua
YH
Li
Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
Yu-Ming
YM
Kang
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Guo-Qing
GQ
Zhu
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects*; D002787:Sterol Esterase / Q000378:metabolism*
D004041:Dietary Fats; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D007545:Isoproterenol
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