Premium
Effects of Highly Active Antiretroviral Therapy (HAART) on adipocyte differentiation in Murine 3T3‐L1 and Primary Human Adipocytes
Author(s) -
Lee Yun Kyung,
Pearson Laurel,
Frank Jennifer,
Nerurkar Vivek R.,
Nerurkar Pratibha V.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a295-c
Subject(s) - lipodystrophy , perilipin , adipocyte , resistin , nucleoside reverse transcriptase inhibitor , biology , nucleoside , medicine , endocrinology , adiponectin , adipose tissue , virology , viral load , antiretroviral therapy , virus , insulin , insulin resistance , biochemistry
Treatment of HIV infection with highly active antiretroviral therapy (HAART) has dramatically reduced morbidity and mortality. HAART includes protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI) and non‐nucleoside reverse transcriptase inhibitors (NNRTI). However, long‐term usage of HAART is associated with lipodystrophy, characterized by increased visceral fat and peripheral lipoatrophy. While PI inhibit transcription factors, peroxisome proliferator‐activated receptor £^ (PPAR£^) and sterol regulatory element‐binding protein 1 (SREBP1c), NRTI reduces mtDNA, leading to mitochondrial toxicity. The objective of our study was to investigate the combined effects of PI (ritonavir, RTV; lopinavir, LPV/r) and NRTI (combivir, CBV) on adipocyte differentiation and expression of PPARƒ× and SREBP1c‐regulated genes, perilipin and resistin in 3T3‐L1 mouse and primary human adipocytes. Our data indicates that RTV, LPV and CBV, significantly increased adipocyte differentiation in mouse adipocytes with a concomitant increase in both, resistin and perilipin mRNA expression in mouse and human adipocytes. A better understanding of the molecular mechanisms will lead to the discovery of new therapeutic molecular targets that will reduce the adverse effects in HIV patients. [Supported by RCMI Program NCRR (G12RR003061), Hawaii Community Foundation (200112061)]