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.

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

BACKGROUND: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH). DESIGN: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA). RESULTS: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals. CONCLUSION: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

Klotho-HIV and Oxidative Stress: The Role of Klotho in Cardiovascular Disease Under HIV Infection-A Review.

Combined antiretroviral therapy has improved quality and life expectancy of people living with human immunodeficiency virus (HIV). However, this therapy increases oxidative stress (OS), which in turn causes alterations in lipid and carbon metabolism, kidney disease, liver cirrhosis, and increased risk of cardiovascular disease. The Klotho gene has been implicated in cardiovascular risk increase. Klotho protein expression at X level decreases the risk of heart disease. HIV-positive people usually present low plasma levels of Klotho; thus, contributing to some extent to an increase in cardiovascular risk for these types of patients, mostly by favoring atherosclerosis. Therefore, our aim is to provide an overview of the effect of OS on Klotho protein and its consequent cardiometabolic alterations in HIV-positive patients on antiretroviral therapy.