PT  - JOURNAL ARTICLE
AU  - Patrick J. Ferrara
AU  - Xin Rong
AU  - J. Alan Maschek
AU  - Anthony R.P. Verkerke
AU  - Piyarat Siripoksup
AU  - Haowei Song
AU  - Karthickeyan C. Krishnan
AU  - Jordan M. Johnson
AU  - John Turk
AU  - Joseph A. Houmard
AU  - Aldons J. Lusis
AU  - James E. Cox
AU  - Saame Raza Shaikh
AU  - Peter Tontonoz
AU  - Katsuhiko Funai
TI  - The Lands cycle modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle
AID  - 10.1101/2019.12.23.887232
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 2019.12.23.887232
4099  - http://biorxiv.org/content/early/2019/12/23/2019.12.23.887232.short
4100  - http://biorxiv.org/content/early/2019/12/23/2019.12.23.887232.full
AB  - Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analyses of primary myocytes from lean insulin-sensitive (LN) and obese insulin-resistant (OB) individuals revealed several species of lysophospholipids (lyso-PL) that were differentially-abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lyso-PC/PC, concomitant with greater insulin sensitivity in vivo and insulin-stimulated skeletal muscle glucose uptake ex vivo. Absence of LPCAT3 reduced phospholipid packing of the cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.