Obesity development in caspase-1-deficient mice

• Published in: International Journal of Obesity 2014-01, Vol.38 (1), p.152-155
• Main Authors: Wang, H, Capell, W, Yoon, J H, Faubel, S, Eckel, R H
• Format: Article
• Language: English
• Subjects: 631/45/127/1213; 692/420; 692/699/2743/393; Animals; Biological and medical sciences; Body Weight; Caspase 1 - deficiency; Caspase 1 - metabolism; Cytokines; Development and progression; Diabetes; Diet; Diet, High-Fat; Disease susceptibility; Endocrinology; Energy balance; Enzymes; Epidemiology; Female; Health Promotion and Disease Prevention; Inflammation - immunology; Inflammation - pathology; Insulin resistance; Insulin Resistance - immunology; Interleukin-18 - metabolism; Interleukin-1beta - metabolism; Internal Medicine; Laboratory animals; Male; Medical research; Medical sciences; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolic Diseases; Metabolism; Mice; Mice, Knockout; Obesity; Obesity - enzymology; Obesity - etiology; Obesity - metabolism; Plasma; Public Health; Sex Factors; short-communication; Time Factors
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2013.59

Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity. Male and female caspase-1-deficient (caspase-1−/−) and control (wild-type (WT)) mice were fed either a high-fat (HF, 45% of kcal) or a low-fat (LF, 10% of kcal) synthetic diet starting at 6 weeks of age. Caspase-1−/− mice maintained lower but detectable levels of IL-18 compared with WT mice. Plasma IL-1β levels were below the detection limit for both KO and WT mice. Male caspase-1−/− mice gained extra fat mass by 16 weeks on the HF diet, but not until 40 weeks on the LF diet. Female capase-1−/− mice gained more fat by 28 weeks but only on the HF diet. These data indicate that caspase-1−/− mice develop obesity with an age and sex-dependent differences, and only male mice display obesity on LF diet. Overall, this study suggests that the lower level of IL-18 in caspase-1−/− mice might be causing obesity development similarly to IL-18-deficient mice.