title: Obesity development in caspase-1-deficient mice.
abstract: 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.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: W
authors.initials: W
authors.lastname: Capell
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Faubel
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Eckel
mesh_terms: D000818:Animals; D001835:Body Weight; D020170:Caspase 1 / Q000172:deficiency* / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007333:Insulin Resistance / Q000276:immunology; D020382:Interleukin-18 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D020382:Interleukin-18; D053583:Interleukin-1beta; D020170:Caspase 1