We demonstrate whole body inflammation (miR146a-/-) exacerbated inactivity-induced fat gain and glucose dysregulation, while muscle specific MyD88 KO mitigated these outcomes in female mice.  Higher gene expression of Igf1 and decreased expression of Ip6k3 in muscle of MyD88 KO female mice may explain enhancement of glucose uptake in the soleus. Whereas protection from fat accumulation may be related to visceral fat gene changes in adipose tissue expansion (Prc1, Gulp1, Anxa2, Cav2, EHD1), adipose beiging (Fgf10), metainflammation (Hmox1), and genes involved in perfusion.  Of noteworthy to mention, two genes decreased in common between muscle and fat with the ablation of muscle MyD88. These were expression of the negative regulator for GLUT4 translocation, Ralgapa2, and uncharacterized 993011J21Rik2, a potential interferon interacting gene. We conclude that future therapeutic strategies for prevention or treatment of obesity and metabolic disturbances in populations unable to be physically active should focus on further understanding how skeletal muscle inflammation communicates with fat storage depots, and how this cross-talk is influenced by sex hormones. SOURCE: Chris Stubben Huntsman Cancer Institute

Pluto Bioinformatics

GSE138940: Muscle specific MyD88-/-confers a sexual dimorphism protecting female mice from inactivity-induced fat accumulation