Role of caspase-1 in regulation of triglyceride metabolism

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 12; pp. 4810 - 4815
• Main Authors: Kotas, Maya E., Jurczak, Michael J., Annicelli, Charles, Gillum, Matthew P., Cline, Gary W., Shulman, Gerald I., Medzhitov, Ruslan
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.03.2013; National Acad Sciences
• Subjects: Animals; Apoptosis; Biological Sciences; Blood plasma; Caspase 1 - genetics; Caspase 1 - metabolism; Cholesterols; Cytokines; Fasting; Fatty Acids - genetics; Fatty Acids - metabolism; Glucose; Homeostasis; Insulin resistance; Interleukin-1 - genetics; Interleukin-1 - metabolism; Lipid metabolism; Lipid Metabolism - physiology; Lipids; Lipoproteins; Metabolism; Mice; Mice, Knockout; Obesity; Rodents; Triglycerides; Triglycerides - genetics; Triglycerides - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1301996110

Caspase-1 is a cysteine protease that can be activated by both endogenous and exogenous inflammatory stimuli and has been shown to have important functions in processes as diverse as proteolytic activation of cytokines, cell death, and membrane repair. Caspase-1–dependent production of the inflammatory cytokines IL-1 and IL-18 has also been implicated in the regulation of appetite, body weight, glucose homeostasis, and lipid metabolism. Consistent with the emerging views of caspase-1 in metabolic regulation, we find that caspase-1–deficient mice have dramatically accelerated triglyceride clearance, without alteration in lipid production or absorption, and resultant decrease in steady-state circulating triglyceride and fatty acid levels. Surprisingly, this effect is independent of IL-1-family signaling, supporting the concept that caspase-1 influences lipid metabolism through multiple mechanisms, not limited to cytokines.