Obese individuals have increased circulating levels of inflammatory cytokines produced by adipose tissue macrophages. Velmurugan et al. found that adipose tissue macrophages from obese mice had decreased levels of the gasotransmitter H2S, increased calcium signaling, and increased production of proinflammatory cytokines. H2S inhibited a calcium channel, which resulted in reduced calcium entry into macrophages. Thus, inflammatory stimuli lead to the depletion of H2S in adipose tissue, which exacerbates inflammatory responses by resident adipose tissue macrophages.