The development of obesity, which is caused by adipocyte hypertrophy, is influenced by interactions within the adipose tissue between various cells of the immune system such as macrophages, T cells, B cells, innate lymphoid cells, and eosinophils. Natural killer T (NKT) cells are a subset of T lymphocytes that recognize lipid antigens in the context of the CD1d protein and are found in various tissues including adipose tissue. Using CD1d knockout (KO), we previously demonstrated that the CD1d-NKT cell axis plays an important role in the development of high-fat diet-obesity. However, the CD1d⁺ cell type important for interacting with NKT cells during obesity has remained elusive. Since adipocytes as well immune cells in the stromal vascular fraction express CD1d, we considered that adipocytes might be able to present lipid antigens to NKT cells. Indeed, such an interaction was demonstrated between mature adipocytes and NKT cells by several labs, including ours. To determine whether NKT cell-adipocyte interactions affect the development of obesity, we generated mice with an adipocyte-specific deletion of CD1d (Adipoq-cre-Cd1d1^f/f; CD1d-AdKO), and fed these animals with a high-fat diet. CD1d-AdKO mice showed smaller body weight gain and improved insulin sensitivity as compared with control mice.  In adipose tissue of CD1d-AdKO mice, the expression of the pro-inflammatory cytokine IFN-g was reduced whereas expression of the anti-inflammatory adipokine adiponectin was increased. Moreover, accumulation of macrophages was markedly reduced in adipose tissue of CD1d-AdKO mice compared with control mice. These results suggested that the interactions between adipocytes and NKT cells through a presentation of endogenous lipid antigen(s) in the context of CD1d induces production of pro-inflammatory cytokines such as IFN-g which promotes adipose tissue inflammation that contributes to obesity. Results for adipocyte-specific CD1d-AdKO mice and findings obtained with other tissue-specific CD1d-KO mice will be discussed.