ABSTRACT
The prevalence of obesity has increased alarmingly both worldwide and in Korea. This has also dramatically increased the prevalence of chronic obesity-associated diseases, including type 2 diabetes (T2D). Extensive studies on the molecular etiology of T2D have revealed several potential mechanisms by which obesity induces the development of insulin resistance and T2D. One of these is low-grade chronic inflammation. Studies hinting at the existence of this phenomenon were first published about 30 years ago. Ten years later, several seminal papers confirmed its existence, which then led to a rapid and massive escalation of research in this field. Today, the notion that obesity-induced inflammation mediates T2D is now well-accepted. This paper will review the key developments in this field, including the discovery that obesity-induced inflammation and insulin resistance is mainly regulated by adipose tissue-resident immune cells, particularly those in visceral adipose tissue. This review further details the research areas, including (1) the obesity-related factors that induce adipose tissue macrophage (ATM) inflammation, (2) the precise effector functions by which adipose tissue immune cells promote insulin resistance, (3) whether there are early immunological events that have an outsize effect on later events and could be targeted to arrest the development of insulin resistance, (4) the roles played by nonimmunological functions of ATMs and other immune cells, and (5) whether there are noncanonical immune responses to obesity (i.e., immune responses that are unique to obesity and cannot be detected by following the discoveries in the classical immunity field).
ABSTRACT
The prevalence of obesity has increased alarmingly both worldwide and in Korea. This has also dramatically increased the prevalence of chronic obesity-associated diseases, including type 2 diabetes (T2D). Extensive studies on the molecular etiology of T2D have revealed several potential mechanisms by which obesity induces the development of insulin resistance and T2D. One of these is low-grade chronic inflammation. Studies hinting at the existence of this phenomenon were first published about 30 years ago. Ten years later, several seminal papers confirmed its existence, which then led to a rapid and massive escalation of research in this field. Today, the notion that obesity-induced inflammation mediates T2D is now well-accepted. This paper will review the key developments in this field, including the discovery that obesity-induced inflammation and insulin resistance is mainly regulated by adipose tissue-resident immune cells, particularly those in visceral adipose tissue. This review further details the research areas, including (1) the obesity-related factors that induce adipose tissue macrophage (ATM) inflammation, (2) the precise effector functions by which adipose tissue immune cells promote insulin resistance, (3) whether there are early immunological events that have an outsize effect on later events and could be targeted to arrest the development of insulin resistance, (4) the roles played by nonimmunological functions of ATMs and other immune cells, and (5) whether there are noncanonical immune responses to obesity (i.e., immune responses that are unique to obesity and cannot be detected by following the discoveries in the classical immunity field).
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.