title: Perilipin 3 Differentially Regulates Skeletal Muscle Lipid Oxidation in Active, Sedentary, and Type 2 Diabetic Males.
abstract: BACKGROUND
  The role of perilipin 3 (PLIN3) on lipid oxidation is not fully understood.
  
  
  OBJECTIVE
  We aimed to 1) determine whether skeletal muscle PLIN3 protein content is associated with lipid oxidation in humans, 2) understand the role of PLIN3 in lipid oxidation by knocking down PLIN3 protein content in primary human myotubes, and 3) compare PLIN3 content and its role in lipid oxidation in human primary skeletal muscle cultures established from sedentary, healthy lean (leans), type 2 diabetic (T2D), and physically active donors.
  
  
  METHODS
  This was a clinical investigation of 29 healthy, normoglycemic males and a cross-sectional study using primary human myotubes from five leans, four T2D, and four active donors. Energy expenditure, whole-body lipid oxidation, PLIN3 protein content in skeletal muscle tissue, and ex vivo muscle palmitate oxidation were measured. Myotubes underwent lipolytic stimulation (palmitate, forskolin, inomycin [PFI] cocktail), treatment with brefeldin A (BFA), and knockdown of PLIN3 using siRNA.
  
  
  METHODS
  Experiments were performed in a Biomedical Research Institute.
  
  
  METHODS
  Protein content, 24-hour respiratory quotient (RQ), and ex vivo/in vitro lipid oxidations.
  
  
  RESULTS
  PLIN3 protein content was associated with 24-h RQ (r = -0.44; P = .02) and skeletal muscle-specific ex vivo palmitate oxidation (r = 0.61; P = .02). PLIN3 knockdown showed drastic reductions in lipid oxidation in myotubes from leans. Lipolytic stimulation increased PLIN3 protein in cells from leans over T2Ds with little expression in active participants. Furthermore, treatment with BFA, known to inhibit coatomers that associate with PLIN3, reduced lipid oxidation in cells from lean and T2D, but not in active participants.
  
  
  CONCLUSIONS
  Differential expression of PLIN3 and BFA sensitivity may explain differential lipid oxidation efficiency in skeletal muscle among these cohorts.
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Covington
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Noland
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: R Caitlin
authors.initials: RC
authors.lastname: Hebert
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Blaine S
authors.initials: BS
authors.lastname: Masinter
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: Pennington Biomedical Research Center (J.D.C., R.C.N., R.C.H., B.S.M., E.R., S.B.), Laboratory of Skeletal Muscle Physiology, Baton Rouge, Louisiana 70808; Louisiana State University Health Sciences Center (J.D.C.), School of Medicine, New Orleans, Louisiana 70112; Translational Research Institute for Metabolism and Diabetes (S.R.S.), Florida Hospital, Sanford-Burnham Medical Research Institute, Winter Park, Florida 32789; Department of Pharmaceutical Biosciences (A.C.R.), University of Oslo, Oslo, Norway; and Department of Kinesiology (S.B.), University of Texas-El Paso, El Paso, Texas 79968.
authors.forename: Sudip
authors.initials: S
authors.lastname: Bajpeyi
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D057185:Sedentary Behavior; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D005576:Colforsin; D019308:Palmitic Acid