ARS | Publication request: Pathophysiology of adipocyte defects and dyslipidemia in HIV lipodystrophy: New evidence from metabolic and molecular studies

Submitted to: American Journal of Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 13, 2005
Publication Date: February 9, 2006
Citation: Balasubramanyam, A., Sekhar, R.V., Jahoor, F., Pownall, H.J., Lewis, D. 2006. Pathophysiology of adipocyte defects and dyslipidemia in HIV lipodystrophy: New evidence from metabolic and molecular studies. American Journal of Infectious Diseases. 2(3):167-172.

Interpretive Summary: Patients infected with HIV are now developing a new condition called HIV lipodystrophy syndrome. This condition is characterized by high blood cholesterol and triglyceride concentrations, which are known to cause cardiovascular disease with time. High blood cholesterol and triglyceride concentrations are usually caused by alterations in fat metabolism. In this paper we discuss the metabolic changes that cause the HIV lipodystrophy syndrome. The data used in the paper is based on our studies performed in HIV -nfected men with HIV lipodystrophy and uninfected healthy men. We found that the patients with HIV lipodystrophy syndrome were removing triglycerides from their circulation much more slowly than the healthy men. They were also storing the triglycerides at a much slower rate. This finding suggested that defective removal from the blood and storage of triglycerides were the causes of high blood triglycerides in patients with HIV lipodystrophy syndrome. We also describe some experiments that suggest that some factors, produced by the blood cells that are infected by the virus, are disrupting the normal function of young and mature fat cells. This alteration of fat cell function in turn seems to be contributing to the dyslipidemia of this syndrome.

Technical Abstract: Despite a burgeoning mass of descriptive information regarding the epidemiology, clinical features, body composition changes, hormonal alterations and dyslipidemic patterns in patients with HIV lipodystrophy syndrome (HLS), the specific biochemical pathways that are dysregulated in the condition and the molecular mechanisms that lead to their dysfunction, remain relatively unexplored. In this paper, we review studies that detail the metabolic basis of the dyslipidemia - specifically, the hypertriglyceridemia - that is the serologic hallmark of HLS and present new data relevant to mechanisms of dyslipidemia in the postprandial state. We also describe preliminary experiments showing that in addition to the well-known effects of highly-active antiretroviral drugs, the functional disruption of adipocytes and preadipocytes by factors intrinsic to HIV-infected immunocytes may play a role in the pathogenesis of HLS.