The molecular regulation of visceral and subcutaneous adipose tissue lipolysis by AMP-activated protein kinase

This study investigated the role of AICAR-induced AMPK activation in the regulation of lipolysis in isolated visceral (VC; epididymal and retroperitoneal) and subcutaneous (SC; inguinal) rat adipocytes and the potential molecular mechanisms involved in this process. AMPK and ACC phosphorylation, basal and epinephrine-stimulated glycerol release, and HSL phosphorylation and activity were determined. AICAR-induced AMPK activation inhibited basal glycerol release by ∼40%, and almost completely prevented epinephrine-stimulated glycerol release in adipocytes from all fat depots. Compound C, an inhibitor of AMPK, prevented AICAR-induced phosphorylation of AMPK and significantly increased basal (∼1.3-, ∼1.4-, and ∼1.7-fold) and epinephrine-stimulated (∼1.3-, ∼1.2-, and ∼1.4-fold) glycerol release in epididymal, retroperitoneal, and inguinal adipocytes, respectively. AICAR increased phosphorylation of HSLSer565 and inhibited epinephrine-induced phosphorylation of HSLSer563 and HSLSer660. This was also accompanied by a 73% reduction in epinephrine-stimulated HSL activity. Compound C prevented the phosphorylation of HSLSer565 induced by AICAR and partially prevented the inhibitory effect of this drug on basal and epinephrine-stimulated lipolysis in VC and SC adipocytes. In summary, despite different fat depots eliciting distinct rates of lipolysis, acute AICAR-induced AMPK activation suppressed HSL phosphorylation/activation and exerted a similar anti-lipolytic effect on both VC and SC adipocytes.