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Published on: August 16, 2020
Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice
Masashi Satoh1, Miyuki Hoshino1, Koki Fujita1
1Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
Abstract:
It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity.
Insights
Adipocytes expressing CD1d interact with NKT cells, worsening obesity and insulin resistance. Deleting CD1d in adipocytes improved metabolic health and reduced inflammation in mice on a high-fat diet.
Area of Science:
- Immunology
- Metabolic Diseases
- Adipose Tissue Biology
Background:
- CD1d expression and NKT cells are implicated in obesity and insulin resistance.
- The specific CD1d-expressing cells mediating these effects are not fully understood.
Purpose of the Study:
- To investigate the role of CD1d-expressing adipocytes in NKT cell-mediated obesity and insulin resistance.
- To define the cellular interactions driving adipose tissue inflammation and dysfunction.
Main Methods:
- Utilized 3T3-L1 adipocytes to study NKT cell interactions and cytokine production.
- Generated adipocyte-specific CD1d-deficient mice for high-fat diet (HFD) feeding studies.
- Assessed adipose tissue mass, insulin sensitivity, NKT cell activation, IFN-γ levels, adiponectin expression, and macrophage recruitment.
Main Results:
- 3T3-L1 adipocytes present ligands to NKT cells, inducing IFN-γ production and altering adipocyte gene expression (increased CD1d, CCL2; decreased adiponectin).
- Adipocyte-specific CD1d deletion in mice on HFD reduced visceral adipose tissue mass and improved insulin sensitivity.
- NKT cell activation, IFN-γ production, and macrophage recruitment were reduced, while adiponectin levels increased in CD1d-deficient mice.
Conclusions:
- Adipocyte CD1d and NKT cell interactions are critical drivers of obesity-induced adipose tissue inflammation and dysfunction.
- Targeting adipocyte CD1d may offer a therapeutic strategy for metabolic disorders like obesity and insulin resistance.
