Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity

Abstract

Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which contributes to, or might be driven by chronic, low-grade inflammation termed “inflammageing”. In recent years, animal and human studies have started to uncover a role for immune cells within the stromal fraction of adipose tissue in driving the health complications that come with obesity, but relatively little work has been conducted in the context of immunometabolic adipose function in ageing. It is now clear that aberrant immune function within adipose tissue in obesity—including an accumulation of pro-inflammatory immune cell populations—plays a major role in the development of systemic chronic, low-grade inflammation, and limiting the function of adipocytes leading to an impaired fat handling capacity. As a consequence, these changes increase the chance of multiorgan dysfunction and disease onset. Considering the important role of the immune system in obesity-associated metabolic and inflammatory diseases, it is critically important to further understand the interplay between immunological processes and adipose tissue function, establishing whether this interaction contributes to age-associated immunometabolic dysfunction and inflammation. Therefore, the aim of this article is to summarise how the interaction between adipose tissue and the immune system changes with ageing, likely contributing to the age-associated increase in inflammatory activity and loss of metabolic control. To understand the potential mechanisms involved, parallels will be drawn to the current knowledge derived from investigations in obesity. We also highlight gaps in research and propose potential future directions based on the current evidence.

Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019?

“…In individuals with obesity, there is marked dysregulation of myeloid and lymphoid responses within AT, with associated dysregulation of cytokine profiles (15). Intrinsically bound to this are endocrine and metabolic derangements, including insulin resistance and adipokine dysregulation with dysfunctional lipid and fatty acid metabolism (16). In highly vascularized AT, endothelial and smooth-muscle cells, as well as resident macrophages, exhibit additional perturbations in response to an activated renin angiotensin system at a local level, with attendant depletion and dysfunction of the counterregulatory angiotensin converting enzyme 2 Mas receptor system (17,18).…”

The ABCD of Obesity: An EASO Position Statement on a Diagnostic Term with Clinical and Scientific Implications

“…Epidemiological, clinical, and translational studies over the past decades have provided evidence of the strong link between visceral and ectopic fat and the development of dyslipidemia, insulin resistance, hypertension, atherosclerosis, and adverse cardiac remodeling, among others [20]. Whilst being clear that visceral/ectopic fat accumulation is a major contributor to cardiometabolic risk above and beyond the BMI [24, 25], implementation of fat distribution assessment into clinical practice remains a challenge. For this reason, EASO has recently argued that the simple measure BMI should continue to be used within ICD-11.…”

Mobilising vitamin D from adipose tissue: The potential impact of exercise

“…Adipose tissue comprises heterogeneous cells including adipocytes, various immune cells and preadipocytes. The cellular composition of adipose impacts on adipose inflammation (Bourlier et al 2008) and the secretion of inflammatory mediators (Maury & Brichard 2010), which is particularly pertinent to individuals with obesity as it contributes to systemic low-grade inflammation (Trim et al 2018).…”