Differential effects of sugar and fat on adipose tissue inflammation

Obesity has become a worldwide pandemic. Low grade inflammation initiated from adipose tissue further promotes deterioration of the health of these individuals. However, the early events that lead to the release of inflammatory factors from adipose tissue have not been well characterized. In order to separate out the effects of glucose and lipids on adipose tissue, we used an adipose-specific knockout of txnip mouse model. In the absence of TXNIP, excess basal glucose uptake by adipocytes lead to modestly increased adiposity. We found a clear uncoupling of two events that are generally assumed to be regulated together: adipose macrophage number increase and their activation. Adipocytes exposure to excess glucose led to an increase of macrophage numbers without activation while metabolic rescuing with a ketogenic diet led to macrophage activation without an analogous increase in macrophage count. We identified multiple factors that contributed to the increase in macrophage number including elevated FFA (free fatty acids) and reduced extracellular matrix whereas decreased adiponectin production was associated with macrophage activation. Overall design: eWAT mRNAseq of WT and TXNIP adipose specific KO animals on control and ketogenic diets, mRNAseq of CD64+ cells isolated from eWAT of WT and adipose specific KO animals on control and ketogenic diet