Substrate-Selective Lipolysis Facilitates Unsaturated TAG Accumulation in Obesity.

Sheng, Jianting; Qi, Shaohua; Chan, Michael; Wang, Elaine; Han, Xianlin; Hsueh, Willa A; Yang, Li; Wong, Stephen T C · Diabetes · 2026

basic_science · Level V

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Abstract

Obesity is associated with the enrichment of unsaturated triacylglycerol (TAG) species in adipose tissue, but the mechanism driving this selective lipid accumulation remains unclear. We investigated whether substrate-selective lipolysis contributes to the retention of unsaturated fatty acids (FAs) in obese adipose tissue. Lipidomic profiling revealed predominant enrichment of FA 18:1 and FA 18:2 in midlife-predominant obese adipose TAGs, and functional assays showed that adipose triglyceride lipase preferentially hydrolyzes saturated TAGs under conditions of sufficient substrate supply. These results identify lipase substrate selectivity as a mechanistic contributor to lipid remodeling in obesity and a potential target for modulating adipose lipid turnover.