HIV Fat Redistribution and the Evaluation of Brown Fat
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      The specific aims of this study are to determine whether HIV-infected patients with
      significant fat redistribution and ectopic fat accumulation have increased brown adipose
      tissue using 18F-FDG Positron Emission Tomography techniques.

      Recent studies suggest down regulation of Dicer, a major component of miRNA has an important
      role in the differentiation and function of brown and white adipose tissue and may contribute
      to lipodystrophy. Therefore we will expand on recent research in this area by recruiting
      HIV-infected men with lipodystrophy. We will perform subcutaneous fat biopsies of the
      dorsocervical and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order
      to explore further the question of down regulation of Dicer and its implication on metabolic
      abnormalities in this population.
    

Detailed description: 
      Among individuals infected with HIV, highly active antiretroviral therapy has reduced the
      incidence of morbidity and mortality however, despite recent improvements in newer
      antiretrovirals patients continue to exhibit secondary effects related to body composition
      such as lipoatrophy of the periphery, increased adiposity of the trunk and lipomatosis,
      especially of the dorsocervical spine. Changes in body composition have been reported in
      40-50% of HIV-infected patients. Several studies have shown that antiretroviral therapy
      contributes to changes in body composition and is coupled with increased dyslipidemia,
      insulin resistance and diabetes.

      Accumulation of fat over the dorsocervical spine, or "buffalo" has been reported in 2% to 13%
      of HIV-infected patients. Enlargement of adipose tissue in the dorsocervical region involves
      subcutaneous fat and is therefore unique to fat accumulation of the abdominal area. Guallar
      et al. examined dorsocervical adipose tissue after surgical removal and found that adipose
      tissue in this area showed substantial levels of the marker gene of brown fat, uncoupling
      protein 1 (UCP-1) suggesting there may be brown adipose tissue (BAT) in HIV infected
      individuals with lipomatosis of the dorsocervical spine. Until recently, BAT was known to be
      present in rodents throughout their lifetime and was thought to be present in humans only
      during infancy and early childhood. However, recent studies using 18F-FDG PET-CT have
      confirmed the presence of BAT in adults. Brown adipose tissue is known to affect whole-body
      metabolism and may be related to insulin sensitivity as well as susceptibility to weight
      gain.

      Using 18F-FDG PET techniques, our group has evaluated HIV-infected subjects with lipoatrophy
      and noted there was significantly increased glucose uptake into subcutaneous tissue which may
      suggest presence of BAT in HIV-infected patients. However our previous study did not
      specifically examine areas of BAT in the subjects. Therefore, using 18F-FDG PET-CT in
      addition to fat biopsies we propose to explore the presence of BAT in fat depots among
      HIV-infected patients with fat redistribution, focusing specifically in the cervical area.

      Also, as recent studies suggest down regulation of Dicer, a major component of miRNA has an
      important role in the differentiation and function of brown and white adipose tissue and may
      contribute to lipodystrophy. We will perform subcutaneous fat biopsies of the dorsocervical
      and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order to explore
      further the question of down regulation of Dicer and its implication on metabolic
      abnormalities in this population.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        HIV infected patients with fat redistribution and non HIV controls
      
Biospecimen description: 
      Blood tests will include a complete blood count, creatinine, SGPT TSH and Free T4,
      triglyceride, total, HDL and LDL cholesterol, HIV test, CD4 count (for HIV+ subjects only),
      HIV viral load (for HIV+ subjects only), fasting glucose, 2 hour OGTT, as well as tissue
      samples from fat biopsy.
    
Keywords: HIV; fat redistribution; brown adipose tissue; PET