Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity

Abstract

Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been proposed that invariant Natural Killer T (iNKT) cells play crucial roles in anti-inflammatory responses in obesity. iNKT cells recognize 'lipid' antigens loaded on CD1d of antigen presenting cells and modulate immune responses by secreting Th1 or Th2 type cytokines depending on species of lipid antigens, antigen presenting cell types, and environmental cytokine milieu. However, the regulatory mechanisms of antigen presenting cells for adipose iNKT cell stimulation have not been clearly elucidated. Recently, we have reported that CD1d expressing adipocytes could act as an antigen presenting cell for adipose iNKT cells by characterization of adipocyte-specific CD1d knockout (CD1d) mice. Upon high-fat diet (HFD) feeding, CD1d mice aggravated adipose tissue inflammation and insulin resistance compared with CD1d mice. In this commentary, we provide the additional data of adipocyte CD1d-dependent regulation of adipose iNKT cell responses as well as systemic insulin sensitivity. In addition, we discuss how the interaction between adipocytes and iNKT cells would be regulated with the progression of obesity.

RNF20 Functions as a Transcriptional Coactivator for PPARγ by Promoting NCoR1 Degradation in Adipocytes

“…Given that lipid metabolism is closely associated with glucose metabolism and insulin sensitivity (1,19,21,22), we tested for glucose tolerance and insulin tolerance. While there were no significant differences in glucose and insulin tolerance, as well as ectopic lipid accumulation, between NCD-fed WT and Rnf20 1/2 mice (Supplementary Fig.…”

Regulatory Roles of Invariant Natural Killer T Cells in Adipose Tissue Inflammation: Defenders Against Obesity-Induced Metabolic Complications

“…In obesity, nutritional stresses promote the secretion of inflammatory cytokines and acute-phase reactants including TNF-α, interleukin (IL)-6, and serum amyloid A in WAT. Although WAT simultaneously increases the release of anti-inflammatory cytokines, including IL-4, IL-10, and IL-2 to counteract the unfavorable effects of inflammation, WAT immunity eventually shifts toward an inflammatory state, leading to prolonged inflammation in obesity ( 8 , 9 , 13 ).…”

“…Interestingly, iNKT cells residing in metabolic tissues are promptly activated by non-professional APCs ( 25 , 44 ). Among the APCs in WAT, adipocytes seem to be a efficient non-professional APCs with the highest levels of CD1d in parallel with expression of other factors required for lipid antigen presentation ( 13 , 25 ). As obesity is closely associated with major changes in the lipid repertoire of adipocytes, considerable attention has been directed to the role of adipocyte-derived lipids in the control of WAT inflammation ( 45 – 47 ).…”

“…Among the resident immune cells in WAT, invariant natural killer T (iNKT) cells are regarded as one of the key players linking dynamic changes in adipocyte metabolisms to WAT homeostasis ( 13 ). In the following review, we briefly discuss different molecular and cellular factors involved in the control of WAT immunity in obesity.…”

Autoimmune responses and inflammation in type 2 diabetes

“…CD1d is expressed on adipocytes more than any other MHC molecule and contributes to protection against insulin resistance by activating iNKT cells to produce IL‐2 and IL‐10, which help in maintenance of adipose tissue T regs . Decrease in iNKT cell numbers in obesity leads to accumulation of M1 macrophages and decline in the adipose tissue T reg population 69‐71 …”