Researchers identify the gaseous signaling molecule hydrogen sulfide as an important regulator of the chronic, low-level inflammation caused by obesity that is associated with insulin resistance and the likelihood of developing type 2 diabetes.

In addition to altering metabolism, obesity also stimulates adipose tissue macrophages (ATMs) to secrete inflammatory cytokines into the circulation, which causes chronic systemic inflammation.

Researchers found that, compared to ATMs from lean mice, ATMs from obese mice were depleted of the gaseous signaling molecule hydrogen sulfide (H₂S) and that bacterial lipopolysaccharide also reduced the amount of H₂S in macrophages.

H₂S inhibited Orai3, a component of the store-operated Ca²⁺ entry (SOCE) pathway, in macrophages. Depletion of H₂S disinhibited Orai3, leading to increased Ca²⁺ entry into macrophages and increased inflammatory cytokine production.

Thus, the proinflammatory environment of adipose tissue is associated with the depletion of H₂S in ATMs, which exacerbates inflammation by increasing SOCE in these cells.

http://stke.sciencemag.org/content/8/407/ra128.full