Feeding and fasting controls liver expression of a regulator of G protein signaling (Rgs16) in periportal hepatocytes

Rgs16 is the only RGS gene that is diurnally regulated in liver of ad libitum fed mice. Rgs16 transcription, mRNA and protein are up regulated during fasting and rapidly down regulated after refeeding. Rgs16 is expressed in periportal hepatocytes, the oxygen-rich zone of the liver where lipolysis and gluconeogenesis predominates. Restricting feeding to 4 hr of the light phase entrained Rgs16 expression in liver but did not affect circadian regulation of Rgs16 expression in the suprachiasmatic nuclei (SCN).Rgs16 is one of a subset of genes that is circadian regulated both in SCN and liver. Rgs16 mRNA expression in liver responds rapidly to changes in feeding schedule, coincident with key transcription factors controlling the circadian clock. Rgs16 expression can be used as a marker to identify and investigate novel G-protein mediated metabolic and circadian pathways, in specific zones within the liver.Body weight homeostasis is maintained through complex communications between the brain and peripheral organs [1-8]. Declining body weight during fasting promotes increased food intake and decreased energy expenditure. By contrast, weight gain following several large meals is compensated by decreased food intake and increased energy expenditure. Many of the orexigenic and anorexigenic signals providing dynamic control of energy and body weight homeostasis are conveyed by G protein coupled receptors (GPCRs) in the brain and periphery [5,9,10]. Here, we investigate a novel approach to understand how G protein signaling in liver regulates metabolic activity to maintain body weight and energy balance.The activity cycle of heterotrimeric G proteins revolves around receptor-catalyzed guanine nucleotide exchange and GTP hydrolysis on the Gα subunit. In the inactive state, GαGDP forms a heterotrimeric complex with Gβγ. Hormone binding to GPCRs activates intracellular signaling by catalyzing guanine nucleotide exchange on the Gα subunit [11]. Active GαGTP and Gβγ subunits dissoci