Role of ß-Klotho and Malondialdehyde in Metabolic Disorders, HIV Infection, and Antiretroviral Therapy.

Metabolic alterations, resulting from factors such as obesity or infections (HIV), generate inflammation in the body, affecting the immune system and causing oxidative stress. Prolonged exposure to antiretroviral therapy (ART) conditions the appearance of alterations considered risk factors for metabolic syndrome (MetS), affecting the quality of life in people living with HIV/AIDS (PLWHA). ß-klotho is a protein that can counteract levels of oxidative stress. The aim was to determine the relation of ß-klotho and oxidative stress with metabolic alterations in PLWHA. We hypothesized that levels of ß-klotho and malondialdehyde (MDA) are related in PLWHA on ART with overweight/obesity. As a result of comparing cases versus controls, significant differences were obtained in levels of ß-klotho (p = 0.011), MDA (p < 0.0001), body mass index (p = 0.001), and weight (p < 0.0001). The presence of MetS in PLWHA was 21.2% and 10.6% according to the World Health Organization and ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria, respectively. The founded correlations were of ß-klotho (r = 0.019) and MDA (r = 0.0001), both with CD4+ cells in PLWHA. In controls, ß-klotho was correlated with very low-density lipoprotein (r = 0.035) and atherogenic index (AI; r = 0.037), MDA with AI (r = 0.039), cholesterol, and low-density lipoprotein (r = 0.002). The increase of inflammation in the organism, owing to HIV infection and/or the presence of obesity, conditions metabolic disruption or depletion of elements needed for homeostasis in the human body.

Reduced fibroblast growth factor 21 and ß-Klotho secretion in untreated congenital isolated GH deficiency.

PURPOSES: Increasing evidence suggests that the FGF-Klotho endocrine system and the somatotropic system (pituitary and extra-pituitary GH) may have important metabolic and immune relationships, thus contributing to the pathophysiology of aging-related disorders, including diabetes, atherosclerosis, and cancer. The status of these interactions in isolated GH deficiency (IGHD) is unknown. The objective of this study was to assess the response of both FGF21 and ß-Klotho levels to a standard meal in a homogeneous group of adults with congenital untreated IGHD due to a homozygous mutation in the GHRH receptor gene. METHODS: In a cross-sectional study, we measured the levels of FGF21 and ß-Klotho, before and 30, 60, 120, and 180 min after a standardized test meal in 20 (11 males) IGHD and 20 (11 males) age-matched controls. Areas under the curves (AUC) of FGF21 and ß-Klotho were calculated. RESULTS: Baseline levels of FGF21 were similar, but baseline levels of ß-Klotho were lower in IGHD subjects. The IGHD individuals exhibited lower AUC for FGF21 and ß-Klotho levels than control subjects. There was a positive correlation between IGF1 and ß-Klotho levels in the pooled groups. No correlation was found between IGF1 and FGF21 levels. CONCLUSIONS: Subjects with lifetime, untreated IGHD exhibit reduced FGF21 and ß-Klotho levels response to a mixed meal. This difference may have consequences on metabolism and aging.