Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging

Abstract

Adipose tissue (AT) is the primary energy reservoir organ, and thereby plays a critical role in energy homeostasis and regulation of metabolism. AT expands in response to chronic overnutrition or aging and becomes a major source of inflammation that has marked influence on systemic metabolism. The chronic, sterile inflammation that occurs in the AT during the development of obesity or in aging contributes to onset of devastating diseases such as insulin resistance, diabetes, and cardiovascular pathologies. Numerous studies have shown that inflammation in the visceral AT of humans and animals is a critical trigger for the development of metabolic syndrome. This work underscores the well-supported conclusion that the inflammatory immune response and metabolic pathways in the AT are tightly interwoven by multiple layers of relatively conserved mechanisms. During the development of diet-induced obesity or age-associated adiposity, cells of the innate and the adaptive immune systems infiltrate and proliferate in the AT. Macrophages, which dominate AT-associated immune cells in mouse models of obesity, but are less dominant in obese people, have been studied extensively. However, cells of the adaptive immune system, including T cells and B cells, contribute significantly to AT inflammation, perhaps more in humans than in mice. Lymphocytes regulate recruitment of innate immune cells into AT, and produce cytokines that influence the helpful-to-harmful inflammatory balance that, in turn, regulates organismal metabolism. This review describes inflammation, or more precisely, metabolic inflammation (metaflammation) with an eye toward the AT and the roles lymphocytes play in regulation of systemic metabolism during obesity and aging. © 2017 American Physiological Society. Compr Physiol 7:1307-1337, 2017.

Consuming cholera toxin counteracts age-associated obesity

“…Mice fed with a high level of fats and carbohydrates have been widely used and provided important clues in the interrelated pathology of obesity, inflammation and metabolic diseases [6, 19, 20]. Interestingly, diet- and senescence-induced obesity share many aspects of pathogenesis, which are collectively presented in two recent detailed reviews [57, 58]. One important commonality is that energy-rich diets cause a subclinical, chronic, low-grade systemic inflammatory state, which is similar to what is caused by immunosenescence in both aged animals and humans [57, 58].…”

“…Interestingly, diet- and senescence-induced obesity share many aspects of pathogenesis, which are collectively presented in two recent detailed reviews [57, 58]. One important commonality is that energy-rich diets cause a subclinical, chronic, low-grade systemic inflammatory state, which is similar to what is caused by immunosenescence in both aged animals and humans [57, 58]. In our previous line of research using probiotic bacteria to counteract the deleterious effects of a Western-style obesogenic diet in mice, we observed mice consuming the high-fat diet had a dramatic decrease in the populations of Tregs in mesenteric [8] and mammary lymph nodes [59].…”

“…Another immune cell population of T-lymphocytes, specifically Th17 cells, have also been reported to counteract obesity in mice; however, Th17 cells are proposed to act by shaping a gut microbiota that promotes leanness [57]. Future studies involving gut microbiome analysis may determine in more detail whether consumption of ctB directly affects gut microbial communities.…”

Interventions to restore appropriate immune function in the elderly

“…Adipose tissue expansion with age is also thought of as a major source of inflammation that has a marked influence on systemic metabolism and contributes to the onset of devastating conditions such as insulin resistance, type-2 diabetes, and cardiovascular disorders [ 13 ]. However, during the development of diet-induced obesity or age-associated adiposity, immunocompetent cells infiltrate and proliferate in the adipose tissue.…”

Influence of different rehabilitative aerobic exercise programs on (anti-) inflammatory immune signalling, cognitive and functional capacity in persons with MS – study protocol of a randomized controlled trial

“…It has been suggested that anti-inflammatory properties of exercise depend on two key mechanisms. First, regular exercise reduces visceral fat mass, a major source of inflammation, also known as “metflammation” (indirect effect) [16, 17]. Second, regular exercise and higher physical fitness levels are associated with increased numbers and proportions of circulating anti-inflammatory regulatory T-cells (T regs ) (direct effect) [18].…”