A: The lipolytic pathway in adipose tissue. ATGL, HSL, and MGL act in sequence in the hydrolysis of TG producing FFAs and glycerol.
The acute lipolytic response is regulated by the opposing action of insulin and β-adrenergic signaling (β-AR) acting through
PKA, which activates HSL directly and ATGL indirectly by promoting the release of the ATGL coactivator CGI-58 from PLIN. Independently
of PKA, G0S2 is believed to act as a brake on lipolysis by inhibiting ATGL, which is the rate-limiting lipase. B: Conceptual illustration of the discoveries by Zhang et al. (11) regarding the role of G0S2 in the regulation of energy homeostasis. In the liver, the transition from the fed state to fasting
invokes an increase in G0S2 expression leading to suppression of hepatic lipolysis and acceleration of TG storage. Furthermore,
G0S2 acts to coordinate hepatic substrate utilization by affecting the rates of lipolysis, gluconeogenesis, glycogen breakdown,
and ketogenesis. Conversely, in adipose tissue the transition to fasting reduces G0S2 expression promoting the mobilization
of FFAs and glycerol through increased lipolysis. Upon refeeding, these fasting-induced changes in G0S2 and substrate metabolism
are reversed promoting a net flux of lipids from the liver to storage in adipose tissue. LD, liquid droplet.