BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS: HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS: TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.
BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infectedpatients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infectedpatients on HAART with FRS, another 60 HIV-1-infectedpatients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS:HIV-1-infectedpatients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS:TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infectedpatients on highly active antiretroviral therapy.
Authors: Jiangmei Yin; Maryanne T Vahey; Anlan Dai; Mark G Lewis; Tatiana Arango; Jake Yalley-Ogunro; Jack Greenhouse; Karla Mendoza; Amir Khan; Niranjan Y Sardesai; Walter Weiss; Jack Komisar; Jean D Boyer Journal: J Infect Dis Date: 2012-06-12 Impact factor: 5.226
Authors: Jason DeFuria; Grace Bennett; Katherine J Strissel; James W Perfield; Paul E Milbury; Andrew S Greenberg; Martin S Obin Journal: J Nutr Date: 2009-06-10 Impact factor: 4.798