Effect of DPP-4 inhibitor on chronic adipose tissue inflammation in obesity mouse model

为了了解自然杀伤T(NKT)细胞在脂肪组织炎症中的生理和病理作用，我们对喂饲正常或高脂饮食的C57BL/6J小鼠腹部和皮下脂肪组织中的NKT细胞亚群进行了鉴定。与脾和外周血相比，脂肪组织中的NKT细胞占淋巴细胞的比例更大，而且脂肪组织中的部分NKT细胞表达更高水平的CD69和细胞内干扰素-γ。我们推测，脂肪组织中的NKT细胞可能在其他组织中形成相同的亚群，这些亚群可能参与脂肪组织的炎症。此外，CD69和细胞内干扰素-γ的高表达增加了脂肪组织中某些NKT细胞受到某种生理机制刺激的可能性。干扰素-γ抑制3T3-L1前脂肪细胞的成脂作用。CD1d1在3T3-L1成熟脂肪细胞中表达，并在干扰素-γ刺激下增强。NKT细胞与3T3-L1脂肪细胞共培养后，NKT细胞分泌干扰素-γ增加，脂肪细胞CD1d1表达增加，且呈干扰素-γ依赖性。我们的发现有力地表明，iNKT细胞通过CD1d1和干扰素-γ与脂肪细胞进行通讯。

To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed on normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared to the spleen and peripheral blood, Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that some NKT cells in adipose tissue may be stimulated by some physiological mechanism. IFN-γ suppressed adipogenesis in 3T3-L1 preadipocytes. CD1d1 was expressed in 3T3-L1 mature adipocytes and was enhanced by IFN-γ stimulation. Cocultures of NKT cells and 3T3-L1 adipocytes resulted in increased IFN-γ secretion from NKT cells and increased CD1d1 expression in adipocytes in an IFN-γ-dependent manner. Our findings strongly suggest that iNKT cells communicate with adipocytes via CD1d1 and IFN-γ.