Obesity increases the risk of metabolic syndromes, including diabetes mellitus and cardiovascular diseases, and one of the major drivers of this risk is chronic low-grade inflammation in visceral adipose tissue (VAT). A study now shows how obesity can disrupt a particular subset of metabolically protective regulatory T (Treg) cells in VAT.

First, Li, Elkins and colleagues explored the metabolic pathways that regulate the homeostasis, composition and function of VAT Treg subsets in normal conditions in mice. They found that the cholesterol biosynthesis pathway is specifically upregulated in VAT Treg cells compared with Treg cells in other tissues. Moreover, they discovered that this cholesterol biosynthesis pathway is crucial for Treg cell homeostasis and accumulation in the VAT, given that loss of SREBP2 (a major transcription factor in cholesterol homeostasis) in Treg cells led to a reduction of Treg cells specifically in the VAT, accompanied by increased VAT inflammation and insulin resistance.