SFEBES2009 Poster Presentations Diabetes and metabolism (59 abstracts)
The influence of HIV status and antiretroviral (ARV) therapy on expression of genes related to mitochondrial metabolism in human adipose tissue (AT)
Kirsty McGee 1 , Meg Boothby 2 , Alison Harte 1 , Jeremy Tomlinson 3 , Margaret Hill 1 , Laura Gathercole 2 , Sudhesh Kumar 1 , Mohsen Shahmanesh 2 & Philip McTernan 1
1Warwick Medical School, Clinical Sciences Research Institute, Coventry, UK; 2HIV Medicine, University Hospital Birmingham, Birmingham, UK; 3Division of Medical Sciences, University of Birmingham, Birmingham, UK.
Background and aims: The mechanisms in HIV by which mitochondrial dysfunction occurs, leading to impaired energy homeostasis and metabolic regulation, are unclear; although similarities are noted in T2DM. Therefore, we investigated the effect of HIV status and ARV therapy on several mitochondrial and nuclear encoded genes related to mitochondrial metabolism and energy homeostasis.
Materials and methods: Subcutaneous AT biopsies from the ileac crest were obtained from 15 controls and 34 HIV subjects pre-(naïve) and post- 6 and 18–24 months ARV therapy (HIV: BMI: 25.5(mean±S.D.)±5.0 kg/m2; age: 35.9±9.49 years; control: BMI: 26.8±4.24 kg/m2; age: 34.8±9.7 years). Real time PCR examined genes related to mitochondrial metabolism. All genes were multiplexed with the housekeeping gene 18S.
Results: Our findings determined that in human AT, HIV naïve patients had significantly elevated levels of hCS (*P<0.03), COX3 (*P<0.042), NRF-1 (*P<0.015) and mtCYTB (*P<0.011), compared with healthy controls. Following ARV therapy, there was a significant elevation in expression of TFAM (P<0.004), PGC-lα (*P<0.05), hCS (***P<0.001) and NRF1 (**P<0.002) compared with healthy controls. Gene expression of TFAM continued to increase between HIV treatment naïve and post 6 months ARV treatment (*P<0.03), whilst mtCYTB was significantly reduced (*P<0.03). Interestingly, following ARV therapy for a longer duration (18–24 months), gene expression appeared to significantly decrease in most cases (hCS (**P<0.01), COX3 (**P<0.01), NRF1 (***P<0.001), mtCYTB (**P<0.01), UCP3 (***P<0.001) and COX4 (***P<0.001) versus 6 months treatment), whilst gene expression of PGC-lα (***P<0.001), UCP2 (*P<0.05) and 12 s (***P<0.001) was increased.
Conclusions: HIV patients, prior to ARV treatment increased mitochondrial function compared with non-HIV case controls. Short-term 6 months ARV therapy increased several mitochondrial related genes, whilst mtCYTB, reduced, indicating respiratory gene dysfunction. However long term therapy reduced expression of the majority of genes assessed, suggesting prolonged ARV therapy may impair mitochondrial function and energy metabolism, whilst elevating PGC-lα in attempts to promote mitochondrial biogenesis.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more