Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV Lipodystrophy Syndrome

Oliveira, Sandro Henrique de Souza Dantas; Aarão, Tinara Leila de Souza; Barbosa, Leonardo da Silva; Lisbôa, Paulo Guilherme Souza; Dutra, Claudia Daniele Tavares; Sousa, Lorena Margalho; Quaresma, Juarez Antônio Simões; Libonati, Rosana Maria Feio

doi:10.1016/j.micpath.2014.02.004

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…Potential mechanisms leading to irreversibility of this phenotype are many. One may speculate that, once established, the accumulation of VAT, characterized by hypoxia and high content of activated macrophages [19], may lead to a pro-inflammatory environment, known to influence adipocyte proliferation and differentiation [20]. These events may cause a vicious and self-maintaining circle, resulting in the lack of improvement in VAT accumulation after the discontinuation of TA and/or ddI.…”

Section: Discussionmentioning

confidence: 99%

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

Gelpi

Afzal

Fuchs

et al. 2019

Aids

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Background: Thymidine analogues (TA) and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous (SAT) to visceral (VAT) adipose tissue, which, in turn, is a risk factor for cardiovascular disease (CVD). We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to TA and/or ddI, without exposure, and uninfected controls and the association with CVD risk factors. Methods: 761 PLWH from the COCOMO study and 2,283 age-and sex-matched uninfected controls from the CGPS study were included. PLWH were stratified according to prior exposure to TA and/or ddI. VAT and SAT were determined by abdominal CT-scan. Hypotheses were tested using regression analyses. Results: Exposure to TA and/or ddI was associated with 21.6 cm 2 larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to TA and/or ddI (3.7 cm 2 per year [2.3-5.1]), but not time since discontinuation (-1.1 cm 2 per year [-3.4-1.1]), was associated with VAT. Prior exposure to TA and/or ddI was associated with excess risk of hypertension (aOR 1.62 [1.13-2.31]), hypercholesterolemia (aOR 1.49 [1.06-2.11]), and low HDL (aOR 1.40 [0.99-1.99]). Conclusions: This study suggests a potentially irreversible and harmful association of TA and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low HDL found in PLWH with prior exposure to TA and/or ddI, even years after treatment discontinuation.

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Section: Discussionmentioning

confidence: 99%

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

Gelpi

Afzal

Fuchs

et al. 2019

Aids

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“…While lipodystrophy in treated HIV infection still occurs, obesity prevalence is increasing, and some persons may experience an overlap syndrome with components of both obesity and lipodystrophy. While central lipohypertrophy is associated with increased adipose tissue inflammation and apoptosis[38], further research is needed to understand the intersections of HIV-, ART- and obesity-induced adipose tissue disturbances, and to define whether these intersections may lead to differential clinical consequences in treated HIV infection.…”

Section: Quality and Quantitymentioning

confidence: 99%

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Lake

2017

Curr HIV/AIDS Rep

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Purpose of Review To summarize knowledge of the prevalence, relevant physiology and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions. Recent Findings Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist. Summary Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

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“…In our study, an increase in SAT density was not associated with a significant increase in adiponectin, as it was in men without HIV, further suggesting AT dysfunction in men living with HIV and denser SAT. Untreated HIV infection can lead to decreased adipocyte differentiation and impairment of proteins related to adipocyte metabolism, including adiponectin, which may initiate alterations of AT function that are further amplified by ART (18,37) and/or central lipohypertrophy and result in worsening cardiometabolic risk (38). These findings highlight the importance of early HIV diagnosis and prevention of obesity throughout the lifespan, independent of ART use, as well as the need for better understanding of AT health and its potential clinical implications in people living with HIV.…”

Section: Discussionmentioning

confidence: 99%

“…NRTI exposure causes peripheral fat wasting through mitochondrial toxicity in SAT adipocytes (39). Higher SAT density in tNRTI-exposed persons may represent lipoatrophic AT with decreased adipocyte size and increased fibrosis, macrophage infiltration and inflammation (18,38). Although switching from a tNRTI-based ART regimen to abacavir-or tenofovir-containing regimens has led to some improvement in limb fat quantity as measured by dual-Xray absorptiometry (39,40,41), higher SAT density after controlling for SAT quantity suggests that the detrimental AT effects of tNRTI exposure are incompletely reversible (42,43).…”

Section: Discussionmentioning

confidence: 99%

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity

Lake

Debroy

et al. 2019

European Journal of Endocrinology

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Objectives Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Methods Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. Results HIV+ men had denser SAT (−95 vs −98 HU HIV−, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV−, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV− men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. Conclusions Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

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Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV Lipodystrophy Syndrome

Cited by 12 publications

References 28 publications

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity

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