Ectopic Fat is Linked to Prior Cardiovascular Events in Men With HIV

Orlando, Gabriella; Guaraldi, Giovanni; Zona, Stefano; Carli, Federica; Bagni, P; Menozzi, Marianna; Cocchi, Stefania; Scaglioni, Riccardo; Ligabue, Guido; Raggi, Paolo

doi:10.1097/qai.0b013e31824c8397

Cited by 41 publications

(23 citation statements)

References 23 publications

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“…Expression of Vpr in differentiated adipocytes increased lipolysis and reciprocally altered regulation of PPARγ and GR target genes involved in insulin sensitivity and lipolysis. Diminished WAT mass also occurred without increase in oxidative disposal of fat over 24 hours, indicating that accelerated lipolysis causes ectopic fat deposition in non-adipose organs, as is well described in HIV patients (41–43). Thus, multiple Vpr mechanisms produce lipoatrophy and hyperlipolysis.…”

Section: Discussionmentioning

confidence: 58%

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: 58%

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

et al. 2013

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“…However, when caloric excess persists and fibrosis limits adipocyte expansion, ectopic fat deposition occurs in sites such as the liver and skeletal muscle. Ectopic fat deposition is associated with additional inflammation and metabolic dysregulation[33, 34], including the development of insulin resistance and CVD[35, 36]. Thus, maintaining adipose tissue function, or quality, is critical to preventing immunometabolic consequences of fat dysfunction independent of fat quantity.…”

Section: Quality and Quantitymentioning

confidence: 99%

“…Obesity and visceral adiposity are documented risk factors for CVD and diabetes mellitus (a CVD risk equivalent) in HIV-infected adults[60, 61], and VAT, intrahepatic fat and epicardial fat are all associated with CVD independent of traditional CVD risk factors in this population[36, 61]. Additionally, HIV infection has been associated with increased type 2 diabetes mellitus[62] and CVD[63, 64] risk.…”

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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“…Associations between intra-abdominal VAT and increased metabolic disease risk (including CVD) are well described both in cross-sectional and longitudinal studies [81, 82]. In a cross-sectional study of nearly 600 HIV-infected men on stable ART, greater VAT, liver fat, and epicardial fat were independently associated with CVD after adjusting for traditional CVD risk factors [83]. HIV-infected participants in the CHARTER study with increased visceral adiposity (estimated by waist circumference ≥88 cm in women or ≥102 cm in men) had significantly worse neurocognitive function.…”

Section: Discussionmentioning

confidence: 99%

Fat Matters: Understanding the Role of Adipose Tissue in Health in HIV Infection

Erlandson

Lake

2016

Curr HIV/AIDS Rep

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More than one-third of adults in the United States are obese, and obesity-related disease accounts for some of the leading causes of preventable death. Mid-life obesity may be a strong predictor of physical function impairment later in life regardless of body mass index (BMI) in older age, highlighting the benefits of obesity prevention on health throughout the lifespan. Adipose tissue disturbances including lipodystrophy and obesity are prevalent in the setting of treated and untreated HIV infection. This article will review current knowledge on fat disturbances in HIV-infected persons, including therapeutic options and future directions.

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Ectopic Fat is Linked to Prior Cardiovascular Events in Men With HIV

Cited by 41 publications

References 23 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

Fat Matters: Understanding the Role of Adipose Tissue in Health in HIV Infection

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