Muscle very long-chain ceramides associate with insulin resistance independently of obesity.

ABSTRACT: Lipids, in particular ceramides and diacylglycerols (DAGs), are implicated in insulin resistance (IR), however their precise roles remain unclear. Here, we leverage natural genetic variation to examine muscle lipids and systemic IR in 399 Diversity Outbred Australia mice fed either chow or a high-fat diet. Adipose tissue mass was significantly associated with 55% of muscle lipid features and whole-body insulin sensitivity, with DAGs as the only lipid class enriched in this association. To disentangle the contribution of adiposity and muscle lipids to whole-body insulin sensitivity, we employed two independent approaches: (1) a linear model correcting muscle lipid features for adipose tissue mass to assess their relationship with insulin sensitivity, and (2) stratifying mice into insulin se

SUBMITTER: Madsen S 

PROVIDER: S-EPMC12309502 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature