Adiponectin lowers glucose production by increasing SOGA

Area of Science:

• Metabolic regulation
• Hormone signaling
• Cellular processes

Background:

• Adiponectin lowers glucose production by enhancing liver insulin sensitivity.
• Insulin inhibits glucose production by suppressing autophagy, but adiponectin's mediator, AMPK, stimulates autophagy, creating a conflict.
• This study investigates a novel mediator for adiponectin's inhibition of autophagy.

Purpose of the Study:

• To identify a novel mediator through which adiponectin inhibits autophagy.
• To elucidate the role of this novel mediator in adiponectin's regulation of glucose production.
• To determine the signaling pathways involved in the regulation of this novel mediator.

Main Methods:

• Mass spectrometry to identify novel proteins in adiponectin-treated cells.
• siRNA knockdown to assess the function of the identified protein (SOGA).
• Analysis of autophagosome and lysosome markers, amino acid secretion, and protein response to signaling pathway modulators (AICAR, LY294002).

Main Results:

• A novel protein, suppressor of glucose by autophagy (SOGA), was identified and found to be increased by adiponectin in hepatocytes.
• siRNA knockdown of SOGA abolished adiponectin's inhibition of glucose production and increased markers of autophagy.
• SOGA levels were regulated by insulin signaling (PI3K) and AMPK, and circulating SOGA correlated with adiponectin and insulin activity in humans and mice.

Conclusions:

• Adiponectin inhibits glucose production via SOGA, which suppresses autophagy.
• Adiponectin increases SOGA through the insulin signaling pathway.
• Circulating SOGA serves as a potential biomarker for adiponectin and insulin activity.