While advances in pharmacologic options for HIV treatment have reduced the incidence and severity of ART-induced adipocyte toxicity (principally mitochondrial DNA [mtDNA] depletion and altered gene expression), the persistence of viral proteins in circulation and locally within adipose tissue impairs adipocyte maturation and activity despite suppression of plasma viremia on therapy (2, 7, 29, 57, 163, 186, 196, 236, 260)

While advances in pharmacologic options for HIV treatment have reduced the incidence and severity of ART-induced adipocyte toxicity (principally mitochondrial DNA [mtDNA] depletion and altered gene expression), the persistence of viral proteins in circulation and locally within adipose tissue impairs adipocyte maturation and activity despite suppression of plasma viremia on therapy (2, 7, 29, 57, 163, 186, 196, 236, 260). of CD4+ and CD8+ T cells in adipose tissue, with effects on macrophage activation and local inflammation, while the presence of latently-infected CD4+ T cells in adipose tissue may constitute a guarded viral reservoir. This review provides a synthesis of the literature on how HIV computer virus, ART treatment, and host characteristics JMV 390-1 interact to impact adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage. Introduction You will find an estimated 1.2 million persons with human immunodeficiency virus (HIV) contamination in the United States, and millions more around the world (33). Since the identification of HIV as JMV 390-1 the cause of acquired immune deficiency syndrome (AIDS) in the early 1980s, the effects of the HIV computer virus on adipose tissue has been an area of basic and clinical research (9). Prior to the availability of antiretroviral medications, excess fat quantity and distribution served as a prognostic indication of HIV disease progression, nutritional depletion, and susceptibility to opportunistic infections (87, 88, 130, 135, 154, 168, 183, 202, 245). After the introduction of combination antiretroviral therapy (ART) treatment in the mid-1990s, the high prevalence of limb excess fat losing, central lipohypertrophy, and accumulation of ectopic excess fat depots, collectively termed HIV lipodystrophy, among ART-treated patients spurred research into the adverse effects of these medications (6, 17, 29, 31, 78, 91, 211, 226, 251). At present, modern ART regimens with excellent antiviral efficacy, durability against resistance mutations, and fewer toxicities permit HIV patients to survive decades on treatment, but this success is tempered by a rising epidemic of overweight and obesity in the HIV populace and increasing prevalence of cardiovascular, metabolic, and other chronic diseases (96, 124, 132, 165, 182, 234). Both HIV and antiretroviral medications can affect adipose tissue quantity, distribution, and contribution to metabolic homeostasis through effects on adipocytes and stromal-vascular cells (23, 67, 84, 131, 240). While improvements in pharmacologic options for HIV treatment have reduced the incidence and severity of ART-induced adipocyte toxicity (principally mitochondrial DNA [mtDNA] depletion and altered gene expression), the persistence of viral proteins in blood circulation and locally within adipose tissue impairs adipocyte maturation and activity despite suppression of plasma viremia on therapy (2, 7, 29, 57, 163, 186, 196, 236, 260). More recently, the identification of latently-infected CD4+ T cells in adipose tissue has emerged as an important concern for HIV remedy research, and a potential source of chronic adipose tissue immune activation and inflammation via cytokine production and viral protein shedding (2, 43, 44, 47, 198). In this review, we provide a synthesis of the literature on how HIV computer virus, ART treatment, and host characteristics interact to impact adipose tissue distribution and contribution to metabolic health, adipose tissue immunology, and adipocyte maturation, cellular regulation, and energy storage. HIV Contamination and Antiretroviral Therapy Alter Adipose Tissue Distribution and Metabolic Characteristics HIV-associated lipodystrophy is usually a phenotypically heterogeneous, acquired condition that gained wide attention in the HIV treatment and research community following the introduction of the protease inhibitor class of antiretroviral medications in the mid-1990s (23). However, subtle changes in adipose tissue distribution and metabolic characteristics were noted even prior to the introduction of effective combination ART (104, 231). Adipose tissue losing and altered nutrient metabolism were noted to accompany chronic infection and inflammation well before the HIV epidemic, reflecting evolutionarily conserved homeostatic pathways linking immune and metabolic systems (105, 271). Reductions in adipose tissue quantity and JMV 390-1 impaired metabolism are observed in chronic viral and non-viral infections (e.g., tuberculosis), but the presence of similar findings in non-infectious, pro-inflammatory conditions, such as malignancy-induced cachexia, highlights the pathogen-independent aspects of these changes (12, 121, 152, 194, 247, 261). The effects of HIV on adipose tissue are situated within this immune-metabolic sense of balance, which serves as a foundation for further perturbations from antiretroviral toxicity. Changes in adipose tissue distribution in untreated HIV-infection HIV losing, characterized by progressive, unintentional weight loss in the context of CD4+ T cell depletion, was recognized as an adverse prognostic factor since the beginning of the epidemic (34, 135). Broadly, HIV losing is characterized by a triad Mouse monoclonal to CD94 of reduced caloric intake, increased basal metabolic rate, and a negative protein balance leading to loss of both excess fat and slim tissue mass. The effects of elevated interleukin (IL)-1, IL-6, and.