Prevalence, underlying mechanisms and role of nutrition in the management of the HIV-associated lipodystrophy syndrome

Student thesis: Doctoral ThesisDoctor of Philosophy


HIV-associated lipodystrophy syndrome (HALS) is characterised by abnormalities of body fat distribution and metabolism resulting from adipocyte dysfunction. This thesis examines the hypothesis that antiretroviral drugs (ARVs) alter PPAR-γ, which contributes to adipocyte dysfunction. We hypothesise that conjugated linoleic acid (CLA) isomers, as putative PPAR-γ ligands, will attenuate adipocyte dysfunction and HALS. In vitro, ritonavir (RTV; 20 μM) was the most potent ARV and significantly decreased triglyceride storage (P < 0.001), perilipin (P = 0.003) and Cidea expression (P < 0.001), PPAR-γ expression (P = 0.014) and nuclear binding (P = 0.03), and adiponectin secretion (P < 0.001) compared with control. Microarray analysis revealed adipocyte differentiation as a top pathway affected by RTV (P = 0.007). The addition of both c9,t11 and t10,c12 (100 μM) to RTV-treated cells in vitro significantly increased triglyceride accumulation compared with control (P < 0.001). c9,t11 increased PPAR-γ nuclear binding (P = 0.038), while t10,c12 decreased perilipin expression (P = 0.004) and adiponectin expression (P = 0.038) and protein secretion (P = 0.003). Although c9,t11 had positive effects on adipocyte function, t10,c12 enhanced the detrimental effects of RTV. The prevalence of HALS was found to be 29% among a cohort of UK patients with HIV. Receiving a first line ARV regimen was associated with reduced odds of developing HALS (OR 0.28, P = 0.003). A study was conducted to investigate the effect of CLA (3 g/d) versus placebo (high-oleic sunflower oil) on abdominal obesity in HIV-infected men. Five of 478 patients were eligible and completed the study. No difference in WC was detected between the groups after 12 weeks of supplementation. Information collected as part of this study will help inform future polyunsaturated fatty acid interventions among HIV patients. The findings of this thesis are discussed in the context of existing scientific literature in the area.
Date of Award2015
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorAnne Mullen (Supervisor) & Sandra O'Dell (Supervisor)

Cite this