What are the relative contributions of NRTIs and protease inhibitors to lipodystrophy?
Mallal, S. (2000) What are the relative contributions of NRTIs and protease inhibitors to lipodystrophy? In: 4th International Conference on Nutrition and HIV infection/2nd European Workshop on Lipodystrophy, 19 - 21 April 2001, Cannes, France.
In vitro studies have demonstrated that when nucleoside analogues and protease inhibitors are combined in cell culture with adipocytes, there appears to be an increased lipolysis (cell decomposition) from those fat cells. The impact of nucleoside analogues on mitochondria could further contribute to diminished cellular energy production - hence diminished transporter activity and may also contribute to release of mitochondria factors that lead to cellular apoptosis (cell death). Biopsy studies performed on individuals at his clinic presented during this meeting indicated a diminution of mitochondrial DNA content and an increase in mitochondrial protein mass in individuals receiving antiretroviral therapy with fat wasting. He proposed that the decrease in mitochondria DNA represents the inhibition in mitochondria polymerase gamma by nucleoside analogues and the compensatory mechanisms within the cell which normally lead to an increase in mitochondrial numbers were driving increased mitochondrial division that was leading to an increased production in mitochondrial protein. In the absence of mitochondrial DNA, these new and enlarged abnormal mitochondria were unlikely to be the efficient energy producing powerhouses that normally exist within human cells. Data is now required to evaluate whether this is the case or whether the increase in mitochondrial protein production reflects an increased cellular energy need as the adipocye (fat cell) struggles with increased fat cycling - an abnormality previously reported by researches at Baylor College, Texas. In this case the diminution of DNA may simply reflect an artefact of sampling, i.e.a relative reduction not an actual reduction.
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|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
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