In obesity, adipose tissue secretes reduced amounts of adiponectin and increased leptin, resistin, and pro-inflammatory cytokines. The net biochemical consequence on hepatic glucose production is:

• A Decreased hepatic glucose production due to increased AMPK activation
• B Decreased hepatic gluconeogenesis due to excess fatty acid oxidation generating excess NADH
• C Unaffected hepatic glucose production as adipokines do not cross hepatic sinusoids
• D Increased hepatic glucose production due to insulin resistance and reduced adiponectin-mediated AMPK activation ✓

Explanation

Adiponectin activates AMPK in the liver, which phosphorylates and inactivates ACC (acetyl-CoA carboxylase), reducing malonyl-CoA and fatty acid synthesis; AMPK also phosphorylates and reduces TORC2 coactivation of CREB, thereby suppressing PEPCK and G6Pase expression (gluconeogenic enzymes). In obesity, adiponectin levels fall and insulin resistance develops, leading to unrestrained hepatic gluconeogenesis and increased fasting hepatic glucose production — the primary driver of fasting hyperglycemia in type 2 DM. Elevated TNF-alpha and IL-6 from obese adipose tissue further impair hepatic insulin signaling.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.