Obesity development in caspase-1-deficient mice.

Area of Science:

• Immunology
• Metabolism
• Obesity Research

Background:

• Caspase-1 is an intracellular cysteine protease crucial for inflammation by activating IL-1β and IL-18.
• Interleukin-18 (IL-18) and IL-1β play roles in energy balance, with IL-18 deficiency linked to obesity and insulin resistance.

Purpose of the Study:

• To investigate whether caspase-1 deficiency leads to obesity.
• To explore the potential role of reduced IL-18 levels in caspase-1 knockout mice regarding obesity.

Main Methods:

• Comparison of caspase-1-deficient (caspase-1-/-) and wild-type (WT) mice of both sexes.
• Feeding mice either a high-fat (HF) or low-fat (LF) diet from 6 weeks of age.
• Monitoring body composition and measuring plasma cytokine levels (IL-18, IL-1β).

Main Results:

• Caspase-1-/- mice exhibited lower but detectable IL-18 levels; IL-1β was below detection limits in all groups.
• Male caspase-1-/- mice showed increased fat mass on HF diets by 16 weeks and on LF diets by 40 weeks.
• Female caspase-1-/- mice gained more fat on HF diets by 28 weeks, but not on LF diets.

Conclusions:

• Caspase-1 deficiency results in obesity with age- and sex-dependent variations.
• Male mice lacking caspase-1 develop obesity on both HF and LF diets, while females do so only on HF diets.
• Reduced IL-18 levels in caspase-1-/- mice may contribute to obesity development, mirroring findings in IL-18-deficient mice.