The Ubiquitin Ligase Siah2 Regulates Obesity-induced Adipose Tissue Inflammation

Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases are essential regulators of inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. In this study, we found that the ubiquitin ligase Siah2 is a central factor in obesity-related adipose tissue inflammation. When challenged with chronic excess energy intake, Siah2-null mice become obese with enlarged adipocytes, but do not develop obesity-induced insulin resistance. Proinflammatory gene expression is substantially reduced in the Siah2-null epididymal adipose tissue of the obese Siah2KO mice. Twelve samples from four groups: WT low fat diet (LFD), WT high fat diet (LFD), Siah2KO LFD, Siah2KO HFD. There are three replicates for each group. For the replicates, equal amounts of RNA from each animal was combined into 3 pools/group for the four groups. The WT LFD, WT HFD and Siah2KO LFD groups each had 10 animals that were combined into 3, 3, or 4 animals/pool. The Siah2KO HFD group had 8 animals that were combined into 3,3, and 2 animals/pool.