title: A characterisation of low-grade inflammation and metabolic complications in HIV-infected patients.
abstract: HIV-associated lipodystrophy syndrome frequently presents as a relative lack of peripheral adipose tissue storage combined with an increase in visceral fat, associated with insulin resistance and dyslipidaemia. This thesis discusses explanations for the links between abnormalities in glucose metabolism, the steroid synthesis pathway, the growth hormone-insulin growth factor-1 axis, and chronic changes in adipose tissue distribution. Specifically, the mechanisms by which low-grade inflammation may affect the normal stimulatory effect of insulin on glucose and fat storage are reviewed. We propose that both chronic low-grade inflammation from HIV infection and treatment with HAART trigger cellular homeostatic stress responses with adverse effects on glucose metabolism. The physiological outcome is such that the total energy storage in the adipocytes is decreased, and the remaining adipocytes resist further energy storage. The excess circulating and dietary lipid metabolites, normally metabolised by adipose tissue, are deposited ectopically in the muscle, liver, or visceral adipose tissue, where they impair insulin action. This deposition of lipid metabolites leads to a vicious circle of insulin resistance and lipotoxicity leading to lipoatrophy or a mixed-type with increased visceral adipose tissue and a clinical phenotype of HIV-associated lipodystrophy syndrome with an elevated waist-to-hip ratio. This HIV-associated inflamm-ageing syndrome can provide a platform for further studies in HIV-infected patients and act as a model for biological accelerated ageing.
authors.affiliation: ove.andersen.privat@gmail.com.
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
mesh_terms: D014943:Global Health; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D008659:Metabolic Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D009017:Morbidity / Q000639:trends; D012720:Severity of Illness Index