Repetitive amiodarone administration causes liver damage via adipose tissue ER stress-dependent lipolysis, leading to hepatotoxic free fatty acid accumulation
Einav Hubel, Sigal Fishman, Minna Holopainen, Reijo Käkelä, Ortal Shaffer, Inbal Houri, Isabel Zvibel, Oren Shibolet
2021American Journal of Physiology-Gastrointestinal and Liver Physiology36 citationsDOIOpen Access PDF
Abstract
AMD chronic administration induces hepatic lipid accumulation by several mechanisms, including induction of hepatic ER stress, impairment of β-oxidation, and inhibition of triacylglycerol secretion. Our study shows that repetitive AMD treatment induces not only hepatic ER stress but also adipose tissue ER stress and lipolysis and hepatic accumulation of free fatty acids and enrichment of palmitate in the total lipids. Understanding the toxicity mechanisms of AMD would help devise ways to limit liver damage.
Topics & Concepts
Adipose tissueLipolysisLipogenesisLipotoxicityEndocrinologyInternal medicineSteatosisAdipose triglyceride lipaseUnfolded protein responseFatty liverChemistryPerilipinEndoplasmic reticulumLiver injuryBiologyInsulin resistanceMedicineBiochemistryInsulinDiseaseEndoplasmic Reticulum Stress and DiseaseAdipose Tissue and MetabolismLipid metabolism and biosynthesis