Remodeling glycerophospholipids affects obesity-related insulin signaling in skeletal muscle

Research output: Contribution to journalReview articlepeer-review


It has long been known that fatty acids can either adversely or positively affect insulin signaling in skeletal muscle, depending on chain length or saturation, and can therefore be primary drivers of systemic insulin sensitivity. However, the detailed mechanisms linking fatty acids to insulin signaling in skeletal muscle have been elusive. In this issue of the JCI, Ferrara et al. suggest a model whereby membrane lipid remodeling mediates skeletal muscle insulin sensitivity. The authors demonstrate that membrane glycerophospholipid fatty acid remodeling by lysophosphatidylcholine acyltransferase 3 (LPCAT3) in skeletal muscle from subjects with obesity was induced, suppressing insulin signaling and glucose tolerance. Loss or gain of LPCAT3 function in mouse models showed that Lpcat3 was both required and sufficient for high-fat diet-induced muscle insulin resistance. These results suggest that the physiochemical properties of muscle cell membranes may drive insulin sensitivity and, therefore, systemic glucose intolerance.

Original languageEnglish (US)
Article numbere148176
JournalJournal of Clinical Investigation
Issue number8
StatePublished - Apr 15 2021

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Remodeling glycerophospholipids affects obesity-related insulin signaling in skeletal muscle'. Together they form a unique fingerprint.

Cite this