HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome.

Abstract
HIV-associated lipodystrophy or lipoatrophy, unreported before the introduction of highly active antiretroviral therapy (HAART), was first described in 1998, and has a prevalence ranging from 18% to 83%. As in genetic lipodystrophy syndromes, fat redistribution may precede the development of metabolic complications (dyslipidemia, insulin resistance) in HIV-infected patients receiving HAART. The pathogenesis of HAART-associated lipodystrophy and metabolic syndrome is complex and a number of factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, and mitochondria. Protease inhibitors are responsible for a decrease in cytoplasmic retinoic-acid protein-1, in low density lipoprotein-receptor-related protein and in peroxisome proliferator activated receptor type-gamma. Nucleoside reverse transcriptase inhibitors, and thymidine analogues, are responsible for mitochondrial dysfunction as demonstrated by a decrease in subcutaneous adipose tissue mitochondrial DNA content. Both phenomena are responsible for a decreased differentiation of adipocytes, increased levels of free fatty acids and lipoatrophy. The increased levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-6 may further contribute in development of lipodystrophy. TNF-alfa activates 11-beta-hydroxysteroid dehydrogenase type-1, which converts inactive cortisone to active cortisol, resulting in increased lipid accumulation in adipocytes and insulin resistance. HAART drugs and inflammatory cytokines are associated with a decrease in adiponectin. The levels of adiponectin and adiponectin-to-leptin ratio correlate positively with insulin resistance in HIV-infected patients with lipodystrophy. HAART-associated metabolic syndrome is an increasingly recognized clinical entity. The atherogenic profile of this syndrome may increase the risk of cardiovascular disease even in young HIV-infected patients. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients receiving HAART.
AuthorsGiuseppe Barbaro
JournalCurrent pharmaceutical design (Curr Pharm Des) Vol. 13 Issue 21 Pg. 2208-13 ( 2007) ISSN: 1873-4286 [Electronic] United Arab Emirates
PMID17627554 (Publication Type: Journal Article, Review)
Chemical References
  • Adiponectin
  • HIV Protease Inhibitors
  • Tumor Necrosis Factor-alpha
Topics
  • Adiponectin (physiology)
  • Animals
  • Antiretroviral Therapy, Highly Active (adverse effects)
  • Cardiovascular Diseases (etiology)
  • HIV Protease Inhibitors (adverse effects)
  • Humans
  • Insulin Resistance
  • Intra-Abdominal Fat (drug effects)
  • Lipodystrophy (chemically induced)
  • Metabolic Syndrome (chemically induced)
  • Tumor Necrosis Factor-alpha (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: