Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 311, Issue 5, Pages E881-E890Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00174.2016
Keywords
adipocytes; cytokines: inflammasome; macrophages; stromal vascular fraction
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Funding
- Japan Society for the Promotion of Science (JSPS)
- MEXT-supported program for the Strategic Foundation at Private Universities
- Astellas Foundation for Research on Metabolic Disorders
- Daiwa Securities Health Foundation
- Pancreas Research Foundation of Japan
- Salt Science Research Foundation of Japan
- Grants-in-Aid for Scientific Research [15K09146, 16H01395, 26461386, 16K19544] Funding Source: KAKEN
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Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1 beta and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat dietinduced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity.
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