Abstract
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.
Highlights
IL37, exits[12,13]
We report that the IL18/IL18R1 system plays an important role on energy homeostasis
The primary finding is that deletion of the ligand or the receptor leads to divergent responses in Brown AT (BAT) and iWAT in terms of beige reprogramming
Summary
IL37, exits[12,13]. the complex IL37/ IL18R1 does not bind IL18RAP. Data gleaned recently have shown that WAT depots develop brown fat features in response to thermogenic stimuli[26,27] This browning process, more prominent in the inguinal subcutaneous fat (iWAT) than in other visceral fat depot, has attracted considerable interest due to its possible beneficial role on total energy metabolism[28]. The present study aims to clarify the potential adaptive function of IL18 signaling on adipose tissue metabolism under different thermogenic stimuli: HFD and cold. For this purpose, we exposed Il18 and Il18r1 deficient mice to HFD and analyzed their metabolic phenotype. The impact of cold-exposure on BAT function and thermal responses was analyzed, as were its effects on brown fat-like gene program in iWAT
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