Diabetes Metab J.  2017 Aug;41(4):229-250. 10.4093/dmj.2017.41.4.229.

Unusual Suspects in the Development of Obesity-Induced Inflammation and Insulin Resistance: NK cells, iNKT cells, and ILCs

• Bonamichi
• Lee J

• KMID: 2392464
• DOI: http://doi.org/10.4093/dmj.2017.41.4.229

Abstract

The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity.

Keyword

Diabetes mellitus, type 2; Innate lymphoid cells; Insulin resistance; Killer cells, natural; Natural killer T-cells; Obesity

MeSH Terms

B-Lymphocytes, Regulatory
Diabetes Mellitus, Type 2
Eosinophils
Humans
Inflammation*
Insulin Resistance*
Insulin*
Intra-Abdominal Fat
Killer Cells, Natural*
Lymphocytes
Macrophages
Metabolism
Models, Animal
Natural Killer T-Cells*
Neutrophils
Obesity
T-Lymphocytes
T-Lymphocytes, Regulatory
Insulin

Figure

• 

  Fig. 1 Innate immunity versus adaptive immunity. NK, natural killer; ILC, innate lymphoid cell; NKT, natural killer T; DC, dendritic cell.

• 

  Fig. 2 Model for the natural killer (NK) cell-mediated regulation of obesity-induced inflammation and insulin resistance. (A) As obesity increases, adipose tissue macrophages (ATMs) become activated and produce chemokines that recruit NK cells from the circulation. This increases the NK cell numbers in epididymal fat. In addition, the obese ATMs produce interleukin 15 (IL-15) and adipocytes produce an as-yet-unknown ligand for natural cytotoxicity triggering receptor 1 (NCR1), which activates the NK cells in epididymal fat. (B) Then, the activated NK cells induce increases in ATM numbers and activation. (C) This cross-activation of ATMs and NK cells induces adipose tissue inflammation in obesity, and eventually adipocyte insulin resistance. Epididymal fat also produces mediators that can regulate insulin resistance in liver and muscle, which eventually leads to the development of systemic insulin resistance. See the text for more details. CCL2, chemokine (C-C motif) ligand 2; TNFα, tumor necrosis factor α.

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