Inhibiting Phosphatidylcholine Remodeling in Adipose Tissue Increases Insulin Sensitivity

Mulin He, Zhiqiang Li, Victoria Sook Keng Tung, Meixia Pan, Xianlin Han, Oleg Evgrafov, Xian Cheng Jiang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cell membrane phosphatidylcholine (PC) composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane PC saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major iso-form of LPCAT in adipose tissue and created adipocyte-specific Lpcat3–knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipo-kine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated PCs in adipocyte plasma mem-branes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissue from ob/ob, db/db, and high-fat diet–fed mice reduced insulin signaling. Adding polyunsaturated PCs to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissue to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.

Original languageEnglish (US)
Pages (from-to)1547-1559
Number of pages13
JournalDiabetes
Volume72
Issue number11
DOIs
StatePublished - Nov 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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