Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels

  • Madeleen Bosma (Creator)
  • Matthijs Hesselink (Creator)
  • Lauren Sparks (Creator)
  • Silvie Timmers (Creator)
  • Maria Ferraz (Creator)
  • Frits Mattijssen (Creator)
  • Denis van Beurden (Creator)
  • Gert Schaart (Creator)
  • Marc DeBaets (Creator)
  • Fons Verheyen (Creator)
  • Sander Kersten (Creator)
  • Patrick Schrauwen (Creator)

Dataset

Description

Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance.
Date made available9 Jun 2012
PublisherWageningen University

Research Output

Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

Catoire, M., Alex, S., Paraskevopulos, N., Mattijssen, F. B. J., Mensink, M. R. & Kersten, A. H., 2014, In : Proceedings of the National Academy of Sciences of the United States of America. 111, 11, p. E1043-E1052

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 64 Citations (Scopus)

    Perilipin 2 improves insulin sensitivity in skeletal muscle despite eleveted intramuscular lipid levels

    Bosma, M., Hesselink, M. K., Sparks, L. M., Timmers, S., Ferraz, M. J., Mattijssen, F. B. J., van Beurden, F., Schaart, G., de Baets, M. H., Verheyen, F. K., Kersten, A. H. & Schrauwen, P., 2012, In : Diabetes. 61, 11, p. 2679-2690 11 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  • 83 Citations (Scopus)

    Cite this

    Bosma, M. (Creator), Hesselink, M. (Creator), Sparks, L. (Creator), Timmers, S. (Creator), Ferraz, M. (Creator), Mattijssen, F. (Creator), van Beurden, D. (Creator), Schaart, G. (Creator), DeBaets, M. (Creator), Verheyen, F. (Creator), Kersten, S. (Creator), Schrauwen, P. (Creator) (9 Jun 2012). Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels. Wageningen University.