Neurotensin promotes hepatic steatosis by regulating lipid uptake and mitochondrial adaptation in hepatocytes.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disease characterized by hepatic steatosis. Mitochondrial dysfunction resulting in the incomplete digestion of surplus fat is one of the key factors that lead to hepatic steatosis but the reason for this remains unclear. We investigated the role of neurotensin (NTS), a gut hormone, in inducing maladaptive fat metabolism in steatotic liver. We identify CD36 and PGC1α, two critical drivers of MASLD, as direct NTS signaling targets in the liver. NTS upregulates CD36, a free fatty acid receptor, in hepatocytes and promotes long chain lipid uptake. Conversely, NTS inhibits PGC1α, which acts as a lipid sensor and translocates to the nucleus to activate lipid catabolism-related genes in an AMPK-dependent manner.

SUBMITTER: Banerjee M 

PROVIDER: S-EPMC12033321 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature