Harris 2015 Diabetes

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Publications in the MiPMap
Harris LA, Skinner JR, Shew TM, Pietka TA, Abumrad NA, Wolins NE (2015) Perilipin 5-driven lipid droplet accumulation in skeletal muscle stimulates the expression of fibroblast growth factor 21. Diabetes 64:2757-68.

» PMID: 25829453 Open Access

Harris LA, Skinner JR, Shew TM, Pietka TA, Abumrad NA, Wolins NE (2015) Diabetes

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.

Bioblast editor: Plangger M O2k-Network Lab: US MO St Louis Abumrad NA

Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Coupling state: OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

Labels, 2018-10