Caspase-1 deficiency reduces intestinal and hepatic triglyceride-rich lipoprotein secretion



Background and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism.
Date made available15 Sep 2013
PublisherWageningen University

Research Output

Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion

van Diepen, J. A., Stienstra, R., Vroegrijk, I. O. C. M., van den Berg, S. A. A., Salvatori, D., Hooiveld, G. J. E. J., Kersten, A. H., Tack, C. J., Netea, M. G., Smit, J. W. A., Joosten, L. A. B., Havekes, L. M., van Dijk, K. W. & Rensen, P. C. N., 2013, In : Journal of Lipid Research. 54, 2, p. 448-456

Research output: Contribution to journalArticleAcademicpeer-review

  • 22 Citations (Scopus)

    Cite this

    van Diepen, J. A. (Creator), Stienstra, R. (Creator), Hooiveld, G. (Creator), Willems van Dijk, K. (Creator), Rensen, P. C. (Creator) (15 Sep 2013). Caspase-1 deficiency reduces intestinal and hepatic triglyceride-rich lipoprotein secretion. Wageningen University.