Adipogenic/Lipid, Inflammatory, and Mitochondrial Parameters in Subcutaneous Adipose Tissue of Untreated HIV-1–Infected Long-Term Nonprogressors

Vidal, Francesc; Domingo, Peré; Villarroya, Francesc; Giralt, Marta; López‐Dupla, Miguel; Gutiérrez, Mar; Gallego-Escuredo, José M.; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Mateo, Gràcia; Guallar, Jordi P; Richart, C

doi:10.1097/qai.0b013e31825c3a68

Cited by 27 publications

(21 citation statements)

References 36 publications

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“…PPARγ positively regulates these genes, indicating that HIV-1 infection per se induces adipose defects via PPARγ repression, consistent with a Vpr effect. Similar gene expression defects occur in fat tissues of HIV-infected, untreated long-term nonprogressors (10) and in mice expressing a 7.7-kb HIV-1 construct (30). …”

Section: Discussionmentioning

confidence: 84%

“…Antiretroviral therapy (ART) drugs have been implicated in some abnormalities (4). However, adverse effects of ART cannot explain key aspects of the phenotype (5); for example, hypertriglyceridemia was noted before the ART era (6), and decreased body fat (7), altered fat distribution (8), and abnormal adipose gene expression (9, 10) occur in untreated patients. Thus, HIV-1 per se could cause adipose dysfunction and associated metabolic defects.…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

et al. 2013

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Viral infections, such as HIV, have been linked to obesity, but mechanistic evidence that they cause adipose dysfunction in vivo is lacking. We investigated a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients tested, including those on antiretroviral therapy (ART) with undetectable viral load. Vpr-mediated mechanisms were dissected in vivo using mouse models expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis, hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots in these mice had diminished mass, macrophage infiltration, and blunted PPARγ target gene expression but increased GR target gene expression. In liver, we observed blunted PPARα target gene expression, steatosis with decreased adenosine monophosphate– activated protein kinase activity, and insulin resistance. Similar to human HIV-infected patients, Vpr circulated in the serum of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally altered association of PPARγ and GR with their target promoters. These results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle control to produce adipose dysfunction and hepatosteatosis. Confirmation of these mechanisms in HIV patients could lead to targeted treatment of the metabolic complications with Vpr inhibitors, GR antagonists, or PPARγ/PPARα agonists.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

et al. 2013

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“…At the same time, adipose tissue is a potential HIV reservoir, leading to recruitment of T lymphocytes and macrophages into adipose tissue. [40] HIV also alters adipocyte differentiation[51, 41, 52]. One proposed mechanisms for this is inhibition of peroxisome proliferator-activated receptor-γ (a regulator of adipogenesis, lipogenesis, insulin sensitivity and normal cytokine/adipokine expression) target gene expression and activation of glucocorticoid target gene expression by the HIV protein Vpr, leading to accelerated lipolysis, increased macrophage infiltration into adipose tissue, diminished white adipose tissue quantity and hepatic steatosis[41].…”

Section: Consequences Of Obesity and Visceral Adipositymentioning

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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“…Additionally, a study of more than 80,000 veterans (27,000 PLWH) found that, after adjusting for Framingham risk, comorbidities, and substance use, PLWH had a 50% increased risk of an acute myocardial infarction (Freiberg et al, 2013). Current dominant hypotheses link the increased incidence of comorbidities to HIV-related chronic inflammation, adipose tissue abnormalities, and modifiable lifestyle factors (e.g., increased tobacco use and decreased physical activity; High et al, 2012; Vidal et al, 2012). Exercise can help prevent and/or mitigate the severity of these chronic comorbidities by improving insulin sensitivity, decreasing visceral fat, mitigating the inflammatory response and oxidative stress, increasing endothelial function, and optimizing lipid profiles (Hand, Lyerly, Jaggers, & Dudgeon, 2009; Kokkinos & Myers, 2010; Kruk, 2007; Roberts & Barnard, 2005; Yahiaoui, McGough, & Voss, 2012).…”

mentioning

confidence: 99%

A Cross-Sectional Description of Age and Gender Differences in Exercise Patterns in Adults Living With HIV

Webel

Barkley

Longenecker

et al. 2015

Journal of the Association of Nurses in AIDS Care

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People living with HIV (PLWH) are living longer and are at greater risk for chronic comorbidities (e.g., cardiovascular disease, cancer) compared to those not living with HIV. Regular, sustained exercise can prevent and/or mitigate the severity of these comorbidities. Our purpose was to describe patterns of planned exercise implemented in the home setting (i.e., free-living exercise) in PLWH by gender and age. PLWH (n = 102) completed a sociodemographic survey and a 7-day exercise diary documenting daily exercise duration, frequency, and intensity. Women exercised an average of 2.4 (IQR: 0.5, 6.0) hours per week compared to men who exercised 3.5 (IQR: 0.5, 7.5) hours per week (p = 0.18). This relationship was particularly evident during middle adulthood for women versus for men (p = 0.05). PLWH exercised regularly but at less than recommended levels. This is among the first evidence describing free-living exercise patterns of PLWH.

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Adipogenic/Lipid, Inflammatory, and Mitochondrial Parameters in Subcutaneous Adipose Tissue of Untreated HIV-1–Infected Long-Term Nonprogressors

Cited by 27 publications

References 36 publications

HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

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

A Cross-Sectional Description of Age and Gender Differences in Exercise Patterns in Adults Living With HIV

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