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

Abstract

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.