Sarcolipin knockout mice fed a high‐fat diet exhibit altered indices of adipose tissue inflammation and remodeling

Objective To investigate indices of adipose tissue inflammation and remodeling in high‐fat diet (HFD) sarcolipin‐knockout ( SLN − /− ) mice. SLN regulates muscle‐based nonshivering thermogenesis and is up‐regulated with HFD. SLN − /− mice develop greater diet‐induced obesity and glucose intolerance. This is accompanied by increases in circulating catecholamines and fatty acids. Catecholamines and fatty acids play a role in the pathology of adipose tissue inflammation. Methods Male mice (wild type and SLN − /− ) were fed a HFD (42% kcal from fat) for 8 weeks. Results SLN − /− mice displayed greater obesity and glucose intolerance. This was accompanied by higher circulating epinephrine and nonesterified fatty acids. Epididymal but not inguinal subcutaneous adipose tissue from SLN − /− mice displayed higher interleukin‐6, suppressor of cytokine signaling 3, interleukin‐1β, and tumor necrosis factor‐α mRNA expression, and this was associated with increased markers of macrophage infiltration (F4/80 expression and crown‐like structures) and M1 polarization (higher CD11c expression and CD11c/MGL1). Interestingly, this occurred despite SLN − /− mice having smaller adipocytes. Conclusions In conditions of nutrient excess, SLN − /− mice display depot‐specific increases in indices of adipose tissue inflammation and remodeling. This could be a compensatory response to reductions in muscle‐based thermogenesis.