Reduced Liver Mitochondrial Energy Metabolism Impairs Food Intake Regulation Following Gastric Preloads and Fasting.

Abstract

The capacity of the liver to serve as a peripheral sensor in the regulation of food intake has been debated for over half a century. The anatomical position and physiological roles of the liver suggest it is a prime candidate to serve as an interoceptive sensor of peripheral tissue and systemic energy state. Importantly, maintenance of liver ATP levels and within- meal food intake inhibition is impaired in human subjects with obesity and obese pre- clinical models. We demonstrate that decreased hepatic mitochondrial energy metabolism in liver-specific, heterozygous PGC1a mice results in reduced mitochondrial response to changes in ΔGATP and tissue ATP following fasting. These impairments in liver energy state are associated with larger and longer meals during chow feeding, impaired dose-dependent food intake inhibition in response to mixed and individual nutrient oral pre-loads, and greater acute fasting-induced food intake. These data support previous work proposing liver-mediated food intake regulation through modulation of peripheral satiation signals.