Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.

Lei Ding,Qi Chen,Feng Zhang,Ming-Xia Zhao,Guo-Qing Zhu,Yue-Hua Li,Xing-Sheng Ren,Yu-Ming Kang

doi:10.1038/srep34374

Lei Ding, Qi Chen + Show 6 more

Open Access

https://doi.org/10.1038/srep34374

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Abstract

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.

Highlights

Primary subcutaneous adipose tissue (SAT) adipocytes derived from normal rats were used to determine whether capsaicin has a direct effect on lipolysis in adipocytes
The results suggest that the lipolysis effect induced by injection of capsaicin into inguinal WAT (iWAT) is attributed to sympathetic activation due to the adipose afferent reflex (AAR) rather than its direct effect on lipolysis
The AAR induced by chemical stimulation of white adipose tissue (WAT) causes a general sympathetic activation[5,11], and the interaction between brain and WAT is likely involved in the control of lipolysis realized by regulating sympathetic activity[21]

Summary

Introduction

Capsaicin-induced AAR caused a greater increase in the HSL phosphorylation at Ser[563] in VAT than that in SAT in Ctrl rats, but not in OB rats (Fig. 3B). Capsaicin-induced AAR caused a greater increase in perilipin phosphorylation level in VAT than that in SAT in Ctrl rats, but not in OB rats (Fig. 3C). Capsaicin-induced AAR increased cAMP levels and PKA activity in both VAT and SAT, but the effect of AAR was smaller in OB rats than that in Ctrl rats.

Results

Conclusion