Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Harris 2015 Diabetes

From Bioblast
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.

ยป 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-ฮฑ, 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.

โ€ข Bioblast editor: Plangger M โ€ข 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