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

Area of Science:

• Metabolic disorders
• Obesity research
• Inflammation

Background:

• Inflammation and metabolic dysfunction are key factors in obesity and type 2 diabetes.
• Caspase recruitment domain (CARD) 9's role in these conditions requires further investigation.

Purpose of the Study:

• To investigate the impact of CARD9 deficiency on high-fat diet-induced obesity in mice.
• To explore CARD9 as a potential molecular therapeutic target for obesity and metabolic disorders.

Main Methods:

• Comparison of CARD9 knockout (CARD9-/-) and wild-type (WT) mice fed normal or high-fat diets for 12 weeks.
• Assessment of glucose tolerance, insulin resistance, oxygen consumption, and heat production.
• Analysis of CARD9/MAPK pathway gene and protein expression in insulin-responsive organs via Western blotting and qPCR.

Main Results:

• CARD9-/- mice exhibited less severe insulin resistance and glucose intolerance compared to WT mice under high-fat diet conditions.
• Absence of CARD9 significantly altered oxygen consumption, carbon dioxide production, and heat generation.
• CARD9-/- mice showed reduced expression of p38 MAPK, JNK, and ERK compared to WT mice.
• High-fat diet increased p38 MAPK, JNK, and ERK in WT mice but not in CARD9-/- mice.

Conclusions:

• CARD9 deficiency confers protection against diet-induced obesity.
• The CARD9/MAPK pathway is implicated in the protective effects observed in CARD9-/- mice.
• Targeting CARD9 may offer a novel therapeutic strategy for managing obesity and related metabolic disorders.