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Abstract
BackgroundLipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.MethodsAnthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.ResultsLeptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.ConclusionThe overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.
Highlights
Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications
The aim of this study was to evaluate the relationship between fat mass, lipodystrophy defined by the Fat Mass Ratio (FMR-L) and the four different categories of fat distribution, and adipocyte derived hormones, orexigenic hormones, prothrombotic factors (PAI-1) and IR in HIV-infected patients on combined antiretroviral therapy (cART)
Adipokines and hormones related to body composition Leptin (Human Leptin RIA Kit, Linco Research), adiponectin (Human Adiponectin RIA Kit, Linco Research), resistin (Human Resistin ELISA Kit, Linco Research), TNF-α (TNF-α IRMA Kit, BioSource), ghrelin (Ghrelin Active RIA Kit, Linco Research) and plasminogen activator inhibitor-1 (PAI-1) (Human PAI-1 ELISA Kit, IBL International GMBH) were measured in the Nobre Laboratory of the Porto Medical School
Summary
Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution. Adipose tissue traditionally was considered an energy storage organ, but over the last decade, it has emerged as a metabolically active endocrine organ secreting multiple bioactive peptides, collectively called “adipokines”, other proteins including inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1), which influence adipocyte function in an autocrine and paracrine fashion, and affect more than one metabolic pathway through the bloodstream’s systemic circulation [3]. These patients experience marked changes in circulating levels of adipocyte secreted hormones, including leptin and adiponectin, contributing to metabolic abnormalities, and hormones related to body composition, such as ghrelin [5]. Low ghrelin may be a marker of metabolic dysregulation and altered body fat without contributing to low GH [6]
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