The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm
Sebastian Larion, Caleb A. Padgett, Joshua T. Butcher, James Mintz, David Fulton, David W. Stepp
2022American Journal of Physiology-Gastrointestinal and Liver Physiology19 citationsDOIOpen Access PDF
Abstract
NAFLD is the most common chronic liver disease, but underlying mechanisms are unclear. We show here that genetically obese ( db/db) mice with fatty liver have impaired hepatic circadian rhythm. Hepatic Per2 expression and PER2 reporter activity are diminished in db/db PER2::LUCIFERASE mice. The biological clock-enhancer nobiletin restores hepatic PER2 in db/db PER2::LUCIFERASE mice, resolving steatosis via downregulation of Srebp1c. These studies suggest targeting the circadian clock may be beneficial strategy in NAFLD.
Topics & Concepts
PER2NobiletinEndocrinologyInternal medicineCircadian rhythmSteatosisCLOCKBiologyLipid metabolismDownregulation and upregulationCircadian clockMedicineBiochemistryFlavonoidGeneAntioxidantCircadian rhythm and melatoninMedicinal Plant ResearchPhytochemicals and Antioxidant Activities