The essential function of CARD9 in diet‐induced inflammation and metabolic disorders in mice

Abstract

Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)‐treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9−/− and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway‐related gene and protein were determined in insulin‐responsive organs using Western blotting and quantitative PCR. The results showed that HFD‐induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9−/− mice. CARD9 absence significantly modified O2 consumption, CO 2 production and heat production. CARD9−/− mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD‐ and ND‐treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9−/− mice. The results indicated that CARD9 absence could be a vital protective factor in diet‐induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet‐induced obesity and metabolism disorder.

CARD9 Signaling, Inflammation, and Diseases

“…CARD9 deficiency with decreased inflammation could be a protective factor in diet‐induced obesity via inhibition of the CARD9/MAPK pathway. In deed, CARD9 KO mice display a reduction in HFD‐induced impairment of glucose tolerance and insulin resistance with decreased expressions of p38 MAPK, JnK, and ERK compared to WT mice ( 109 ). O 2 consumption, CO 2 production, and heat production are also altered in CARD9 KO mice ( 109 ).…”

“…In deed, CARD9 KO mice display a reduction in HFD‐induced impairment of glucose tolerance and insulin resistance with decreased expressions of p38 MAPK, JnK, and ERK compared to WT mice ( 109 ). O 2 consumption, CO 2 production, and heat production are also altered in CARD9 KO mice ( 109 ). CARD9 could contribute to ambient PM 2.5 -induced pulmonary injury in mice through mediating Th17 cell differentiation ( 110 ).…”

The Role of CARD9 in Metabolic Diseases

“…A recent study conducted by Yang et al indicated that CARD9 deficiency mitigated the high fat diet (HFD)-induced metabolic disorders and inflammation by suppressing p38 MAPK and NF-κB signaling pathways [5] . In HFD-treated mice, CARD9 deficiency ameliorated adiposis, diminished the excessive lipid accumulation, and alleviated adiposity-associated symptoms including glucose tolerance impairment, inflammation and hepatopathy.…”

“…Yang et al revealed that CARD9 accelerated the development of IR and increased the activation of p38 and NF-κB in HFD-fed mice [5] . Besides, Cao et al found that CARD9 deficiency retarded the development of IR and decreased p38 activation [6] .…”

“…Currently, extensive studies in terms of the potential involvement of caspase recruitment domain containing protein 9 (CARD9), an upstream molecule of NF-κB, in inflammation have been conducted [3,4] . As a result, CARD9 may be involved in metabolic diseases, which has been proved by some researches [5,6] .…”