The metabolic fate of dietary lipid in Human Immunodeficiency Virus : implications for the development of lipodystrophy
The metabolic fate of dietary lipid in Human Immunodeficiency Virus : implications for the development of lipodystrophy
During recent years, a HIV-associated lipodystrophy syndrome similar to Metabolic Syndrome X has been reported in HIV patients using highly active antiretroviral therapy (HAART). While the metabolic processes that appear to be dysregulated are similar to those of Metabolic Syndrome X (hyperlipidaemia and an altered insulin sensitivity), the changes appear to be more profound. While it is possible that HIV-associated lipodystrophy is related to the presence of infection plus genetic and environmental factors such as high saturated fat intakes, obesity, smoking and lack of exercise, there is a clear distinction between this and Metabolic Syndrome X as in HIV-associated lipodystrophy there is concurrent depot specific fat accumulation and fat wasting. This would suggest that use of HAART in HIV infection results in altered adipocyte metabolism.
In order to investigate peripheral clearance and uptake of lipid from the circulation, stable isotope labelled fatty acids were given to healthy and HIV subjects with and without HAART and with lipodystrophy associated with specific drug combinations. The results suggest that while HIV infection is associated with delayed clearance of lipid from the circulation, the use of HAART exacerbates this process. In addition, it appears that while PI drugs may delay adipocyte clearance of triglyceride from the circulation, NRTI drugs may reduce adipocyte free fatty acid uptake.
An audit of patients with more than six months exposure to HAART (n=545) showed that 25% of patients had elevated plasma lipid, 10% had elevated plasma glucose, but only 9% had both. While this data did not shown an association between specific drug classes and elevated plasma lipid or glucose, there was an association with the duration of therapy. Therefore, it is possible that HAART contributes to the development of HIV-lipodystrophy, but that the cause of this syndrome and the metabolic perturbations are multifactorial.
University of Southampton
Ware, Lisa J
74860e6c-ac74-44ae-bb62-a7a2032852ba
2002
Ware, Lisa J
74860e6c-ac74-44ae-bb62-a7a2032852ba
Ware, Lisa J
(2002)
The metabolic fate of dietary lipid in Human Immunodeficiency Virus : implications for the development of lipodystrophy.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
During recent years, a HIV-associated lipodystrophy syndrome similar to Metabolic Syndrome X has been reported in HIV patients using highly active antiretroviral therapy (HAART). While the metabolic processes that appear to be dysregulated are similar to those of Metabolic Syndrome X (hyperlipidaemia and an altered insulin sensitivity), the changes appear to be more profound. While it is possible that HIV-associated lipodystrophy is related to the presence of infection plus genetic and environmental factors such as high saturated fat intakes, obesity, smoking and lack of exercise, there is a clear distinction between this and Metabolic Syndrome X as in HIV-associated lipodystrophy there is concurrent depot specific fat accumulation and fat wasting. This would suggest that use of HAART in HIV infection results in altered adipocyte metabolism.
In order to investigate peripheral clearance and uptake of lipid from the circulation, stable isotope labelled fatty acids were given to healthy and HIV subjects with and without HAART and with lipodystrophy associated with specific drug combinations. The results suggest that while HIV infection is associated with delayed clearance of lipid from the circulation, the use of HAART exacerbates this process. In addition, it appears that while PI drugs may delay adipocyte clearance of triglyceride from the circulation, NRTI drugs may reduce adipocyte free fatty acid uptake.
An audit of patients with more than six months exposure to HAART (n=545) showed that 25% of patients had elevated plasma lipid, 10% had elevated plasma glucose, but only 9% had both. While this data did not shown an association between specific drug classes and elevated plasma lipid or glucose, there was an association with the duration of therapy. Therefore, it is possible that HAART contributes to the development of HIV-lipodystrophy, but that the cause of this syndrome and the metabolic perturbations are multifactorial.
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Published date: 2002
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Local EPrints ID: 464897
URI: http://eprints.soton.ac.uk/id/eprint/464897
PURE UUID: c97a2a9c-0e24-4fa8-9f10-34eaff25473f
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Date deposited: 05 Jul 2022 00:08
Last modified: 16 Mar 2024 19:48
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Author:
Lisa J Ware
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