title: Perilipin 5-Driven Lipid Droplet Accumulation in Skeletal Muscle Stimulates the Expression of Fibroblast Growth Factor 21.
abstract: Perilipin 5 (PLIN5) is a lipid droplet protein and is highly expressed in oxidative tissue. Expression of the PLIN5 gene is regulated by peroxisome proliferator-activated receptor-α, fasting, and exercise. However, the effect of increased muscle PLIN5 expression on whole-body energy homeostasis remains unclear. To examine this, we developed a mouse line with skeletal muscle PLIN5 overexpression (MCK-Plin5). We show that MCK-Plin5 mice have increased energy metabolism and accumulate more intramyocellular triacylglycerol but have normal glucose and insulin tolerance. MCK-Plin5 mice fed high-fat chow manifest lower expression of inflammatory markers in their liver and increased expression of "browning" factors in adipose tissue. This muscle-driven phenotype is, at least in part, mediated by myokines; the MCK-Plin5 mice have 80-fold higher FGF21 gene expression in muscle and increased serum FGF21 concentration. The increase in FGF21 occurs mainly in muscles with a predominance of fast-twitch fibers, suggesting that fiber type-specific lipid storage may be part of the mechanism conferring metabolic protection in MCK-Plin5 mice. In conclusion, upregulating the PLIN5 level in skeletal muscle drives expression of the FGF21 gene in fast-twitch fibers and is metabolically protective. These findings provide insight into the physiology of PLIN5 and the potential contribution of its upregulation during exercise.
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Lydia-Ann L S
authors.initials: LA
authors.lastname: Harris
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: James R
authors.initials: JR
authors.lastname: Skinner
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Trevor M
authors.initials: TM
authors.lastname: Shew
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Terri A
authors.initials: TA
authors.lastname: Pietka
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.affiliation: Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO nwolins@wustl.edu.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Wolins
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C414620:fibroblast growth factor 21; C551268:lipid storage droplet protein 5, mouse; D005346:Fibroblast Growth Factors
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