title: The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.
abstract: While the 3T3-L1 adipocyte model is routinely used for the study of obesity and diabetes, the mitochondrial respiratory profile in normal versus high glucose has not been examined in detail. We matured adipocytes in normal (5mM) or high (30 mM) glucose and insulin and examined the mitochondrial bioenergetics. We also assessed the requirement for the Unfolded Protein Response (UPR) and ER stress under these conditions. Basal respiration was ~1.7-fold greater in adipocytes that had matured in 30 mM glucose; however, their ability to increase oxygen consumption in response to stress was impaired. Adipogenesis proceeded in both normal and high glucose with concomitant activation of the UPR, but only high glucose was associated with increased levels of ER stress and mitochondrial stress as observed by parallel increases in CHOP and protein succination. Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration. Our data suggests that mitochondrial stress, protein succination and ER stress are uniquely linked in adipocytes matured in high glucose.
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Tanis
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Gerardo G
authors.initials: GG
authors.lastname: Piroli
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Stani D
authors.initials: SD
authors.lastname: Day
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA. Electronic address: norma.frizzell@uscmed.sc.edu.
authors.forename: Norma
authors.initials: N
authors.lastname: Frizzell
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D010654:Phenylbutyrates / Q000494:pharmacology*; D017510:Protein Folding; D051742:Transcription Factor CHOP / Q000032:analysis; D056811:Unfolded Protein Response
chemical_list: C497250:Ddit3 protein, mouse; D010654:Phenylbutyrates; D051742:Transcription Factor CHOP; C075773:4-phenylbutyric acid; D005947:Glucose
keywords: Adipocyte; Diabetes; Fumarate; Phenylbutyrate; Succination; Uncoupler