It used to be thought that BAT was only present in meaningful amounts in infants and that it regressed and become metabolically inactive in adults. Brown adipose tissue (BAT, mainly characterized in rodents) ensures non‐shivering thermogenesis it can maintain thermal homeostasis by dissipating large amounts of energy in the form of heat. The activity of WAT is strongly linked to inflammation in healthy individuals (where low-grade inflammation is required for correct metabolic activity) ( 2), and even more so in ageing and in people with fat gain/obesity (where the more intense inflammation contributes to the loss of metabolic activity) ( 3). White adipose tissue (WAT) is the main site for lipid storage and mobilization and has a high secretion capacity. The various ATs differ with regard to their metabolic activity, sites, plasticity, vascularization and innervation. Lastly, pink adipocytes are white adipocytes that have differentiated into milk-producing gland cells during pregnancy, lactation, and post-lactation ( 1). Beige adipocytes (white adipocytes that have differentiated into brown adipocytes) are characterized by multilocular lipid droplets. Brown adipocytes contain several small lipid droplets and large numbers of mitochondria and lysosomes the latter are responsible for the tissue’s brown color. White adipocytes are characterized by a single, large droplet of cytoplasmic fat and a flattened nucleus. Several “Colors” of Adipose Tissue: White, Brown, Beige, and PinkĪdipose tissue (AT) is a loose connective tissue composed of differentiated adipocytes and stroma/vascular cells (a heterogeneous cell population including endothelial cells, immune cells, fibroblasts, and adipocyte precursors). Besides, reducing ART toxicities remains a crucial therapeutic goal. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT.
During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity.
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