Jeffrey D Covington1, Robert C Noland1, R Caitlin Hebert1, Blaine S Masinter1, Steven R Smith1, Arild C Rustan1, Eric Ravussin1, Sudip Bajpeyi1. 1. 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.
Abstract
CONTEXT: 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. DESIGN, PARTICIPANTS, AND INTERVENTION: 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. SETTING: Experiments were performed in a Biomedical Research Institute. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN, PARTICIPANTS, AND INTERVENTION: 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. SETTING: Experiments were performed in a Biomedical Research Institute. MAIN OUTCOME MEASURES: 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: Jeffrey D Covington; Sudip Bajpeyi; Cedric Moro; Yourka D Tchoukalova; Philip J Ebenezer; David H Burk; Eric Ravussin; Leanne M Redman Journal: Eur J Endocrinol Date: 2014-10-23 Impact factor: 6.664
Authors: Jeffrey D Covington; Jose E Galgani; Cedric Moro; Jamie M LaGrange; Zhengyu Zhang; Arild C Rustan; Eric Ravussin; Sudip Bajpeyi Journal: PLoS One Date: 2014-03-14 Impact factor: 3.240
Authors: S O Shepherd; M Cocks; P J Meikle; N A Mellett; A M Ranasinghe; T A Barker; A J M Wagenmakers; C S Shaw Journal: Int J Obes (Lond) Date: 2017-07-24 Impact factor: 5.095
Authors: Maya Styner; Gabriel M Pagnotti; Cody McGrath; Xin Wu; Buer Sen; Gunes Uzer; Zhihui Xie; Xiaopeng Zong; Martin A Styner; Clinton T Rubin; Janet Rubin Journal: J Bone Miner Res Date: 2017-05-04 Impact factor: 6.741
Authors: Sudip Bajpeyi; Jeffrey D Covington; Erin M Taylor; Laura K Stewart; Jose E Galgani; Tara M Henagan Journal: Endocrinology Date: 2017-07-01 Impact factor: 4.736