title: Short chain fatty acids induce UCP2-mediated autophagy in hepatic cells.
abstract: Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit). In addition, elimination of gut flora by chronic antibiotic treatment diminished basal hepatic autophagy in mice suggesting that gut microbiota can regulate hepatic autophagy. These findings provide novel insights into the interplay between diet, gut microbiota, short chain fatty acids, and hepatic autophagic signaling.
authors: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Caserta, Italy.
authors: Liliana F
authors: LF
authors: Iannucci
authors: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors: Jingfeng
authors: J
authors: Sun
authors: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors: Brijesh K
authors: BK
authors: Singh
authors: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors: Jin
authors: J
authors: Zhou
authors: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Vincent A
authors: VA
authors: Kaddai
authors: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Caserta, Italy.
authors: Antonia
authors: A
authors: Lanni
authors: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: paul.yen@duke-nus.edu.sg.
authors: Paul M
authors: PM
authors: Yen
authors: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: rohit.sinha@duke-nus.edu.sg.
authors: Rohit A
authors: RA
authors: Sinha
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002087:Butyrates / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011422:Propionates / Q000378:metabolism; D000071246:Uncoupling Protein 2 / Q000378:metabolism*
chemical_list: D002087:Butyrates; D005227:Fatty Acids; D011422:Propionates; D000071246:Uncoupling Protein 2
keywords: Autophagy; Microbiome; SCFA; UCP2