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Brown and beige adipocytes recruitment in brown (BAT) or white adipose tissue, mainly in the inguinal fat pad (iWAT), meet the need for temperature adaptation in cold-exposure conditions and protect against obesity in face of hypercaloric diets. Using  interleukin18  ( Il18)  and  Il18 receptor 1 - knockout ( Il18r1 -KO) mice, this study aimed to investigate the role of IL18 signaling in BAT and iWAT activation and thermogenesis under both stimuli.  Il18 -KO, extremely dietary obesity-prone as previously described, failed to develop diet-induced thermogenesis as assessed by BAT and iWAT  Ucp1  mRNA levels. Overweight when fed standard chow but not HFD, HFD-fed  Il18r1 -KO mice exhibited increased iWAT  Ucp1  gene expression. Energy expenditure was reduced in pre-obese  Il18r1 -KO mice and restored upon HFD-challenge. Cold exposure lead to similar results;  Il18r1 -KO mice were protected against acute body temperature drop, displaying a more brown-like structure, alternative macrophage activation and thermogenic gene expression in iWAT than WT controls. Opposite effects were observed in  Il18 -KO mice. Thus,  Il18  and  Il18r1  genetic ablation disparate effects on energy homeostasis are likely mediated by divergent BAT responses to thermogenic stimuli as well as iWAT browning. These results suggest that a more complex receptor-signaling system mediates the IL18 adipose-tissue specific effects in energy expenditure.

Divergent responses to thermogenic stimuli in BAT and subcutaneous adipose tissue from interleukin 18 and interleukin 18 receptor 1-deficient mice