Loss of Lkb1 in CD11c myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance.

Adipose tissue CD11c myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80's expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis while IL-17A promotes the adipogenesis in vitro, which might account in part for the fat gain resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.