Dysfunctional Subcutaneous Fat With Reduced Dicer and Brown Adipose Tissue Gene Expression in HIV-Infected Patients

HIV infection and antiretroviral therapy (ART) use are associated with perturbations in glucose and lipid metabolism. Increasing incidence of diabetes, cardiovascular disease, and obesity highlights the need for early identification and treatment of metabolic dysfunction. Newer ART regimens are less toxic for cellular function and metabolism but have failed to completely eliminate metabolic dysfunction with HIV infection. Additional factors, including viral-host interactions, diet, physical activity, non-ART medications, and aging may further contribute to metabolic disease risk in the HIV setting. We summarize the recent literature regarding the impact on metabolic function of HIV infection, ART, and pharmaceutical or lifestyle prescriptions.

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“…[17] Lipodystrophic PLWH may exhibit dysfunctional SAT and down-regulation of BAT-related genes which would induce metabolic dysfunction. [18]…”

Section: Hiv Infection and Art Can Alter Glucose And Fat Metabolismmentioning

confidence: 99%

Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence

2016

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“…HIV-infected subjects with lipodystrophy are characterized by the presence of excessive dorsocervical fat. Dorsocervical fat accumulation is correlated with the down-regulation of brown and beige fat genes in nonlipomatous abdominal subcutaneous fat (Torriani et al, 2016). These observations indicate that WAT browning is impaired in lipodystrophic HIV patients.…”

Section: Disease-induced Browning Of Watmentioning

confidence: 99%

Inter-organ regulation of adipose tissue browning

Wang

Yang

2016

Cell. Mol. Life Sci.

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Adaptive thermogenesis is an important component of energy expenditure. Brown adipocytes are best known for their ability to convert chemical energy into heat. Beige cells are brown-like adipocytes that arise in white adipose tissue in response to certain environmental cues to dissipate heat and improve metabolic homeostasis. A large body of intrinsic factors and external signals are critical for the function of beige adipocytes. In this review, we discuss recent advances in our understanding of neuronal, hormonal, and metabolic regulation of the development and activation of beige adipocytes, with a focus on the regulation of beige adipocytes by other organs, tissues, and cells. Understanding the cellular and molecular mechanisms of inter-organ regulation of adipose tissue browning may provide an avenue for combating obesity and associated diseases.

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“…The enlargement of the dorsocervical adipose depot (i.e., the ‘buffalo hump’) in ART-treated individuals has been attributed to an ‘energy excess’ state resulting from increased circulating lipids in combination with deficient energy storage in atrophied and fibrotic subcutaneous fat (115, 240). In support of this hypothesis, higher dorsocervical fat accumulation is observed in patients with lower expression of Dicer and other genes associated with brown or beige fat in the subcutaneous tissue (254). Studies of dorsocervical adipose tissue from HIV-infected individuals have shown fibrosis and decreased vascularity, but less dysregulated adipogenesis and in situ inflammation, compared to other subcutaneous fat deposits (16, 35).…”

Section: Hiv Infection and Antiretroviral Therapy Alter Adipose Tissumentioning

confidence: 86%

“…A study of subcutaneous adipose tissue biopsies from patients with HIV-associated lipodystrophy found reduced expression of the endoribonuclease Dicer , which has a role in the differentiation of adipose tissue into a ‘white fat’ versus ‘brown fat’ phenotype (177, 254). White fat functions primarily as an energy storage depot, while brown fat has higher mitochondrial density and a role in thermal regulation.…”

Section: Hiv Infection and Antiretroviral Therapy Alter Adipose Tissumentioning

confidence: 99%

“…Mice with a fat-specific Dicer knockout develop a lipodystrophy characterized by decreased overall white adipose tissue mass, abnormal whitening of interscapular brown adipose tissue, insulin resistance, adipose tissue inflammation, and dyslipidemia; changes similar to those observed in HIV patients (177, 178). In HIV-infected men, subcutaneous abdominal adipose tissue has reduced expression of Dicer and several brown adipose tissue-related genes, including peroxisome proliferator-activated receptor coactivator-α (PPAR-α), PRDM16 (a transcription co-regulator that controls the development of brown adipocytes), and type II iodothyronine deiodinase (DIO2; a deiodinase characteristic of brown fat that converts T4 to active T3 and contributes to thermogenesis) (254). Taken together, these findings indicate subcutaneous fat loss is accompanied by a concurrent a ‘whitening’ of remaining tissue in HIV lipodystrophy, and a shift to a pro-inflammatory and pro-fibrotic state.…”

Section: Hiv Infection and Antiretroviral Therapy Alter Adipose Tissumentioning

confidence: 99%

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Adipose Tissue in HIV Infection

Koethe

2017

Comprehensive Physiology

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HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling. HIV viral proteins persist in circulation and locally within adipose tissue despite suppression of plasma viremia on ART, and exposure to these proteins impairs preadipocyte maturation and reduces adipocyte expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and other genes involved in cell regulation. Several early nucleoside reverse transcriptase inhibitor and protease inhibitor antiretroviral drugs demonstrated substantial adipocyte toxicity, including reduced mitochondrial DNA content and respiratory chain enzymes, reduced PPAR-γ and other regulatory gene expression, and increased pro-inflammatory cytokine production. Newer-generation agents, such as integrase inhibitors, appear to have fewer adverse effects. HIV infection also alters the balance 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 protected viral reservoir. This review provides a synthesis of the literature on how HIV virus, ART treatment, and host characteristics interact to affect adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage.

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Dysfunctional Subcutaneous Fat With Reduced Dicer and Brown Adipose Tissue Gene Expression in HIV-Infected Patients

Cited by 41 publications

References 28 publications

Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence

Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence

Inter-organ regulation of adipose tissue browning

Adipose Tissue in HIV Infection

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