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The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-associated diseases as reported in NLRP3 deficient mice. Here we asked whether in old mice C57BL6J the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age- assocociated metabolic syndrome providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. MCC950 inhibited the Pi3K/AKT/mTOR pathway, and enhanced autophagy and activated peroxisome proliferator-activated receptor alpha (PPARα) in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by mTOR inhibiton activating autophagy and PPARα. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-associated metabolic syndrome.
This article was published in the following journal.
Name: The journals of gerontology. Series A, Biological sciences and medical sciences
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Services for the diagnosis and treatment of diseases in the aged and the maintenance of health in the elderly.
An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A subspecialty of psychiatry concerned with the mental health of the aged.
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