Subcutaneous adipose tissue evaluation and its association with biomarkers of inflammation and energy metabolism in people living with HIV

Author(s)

Mariana Palma Guimarães

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-11-12

Examining board members

Anderson Marliere Navarro; Mariana Kiomy Osako; Rodrigo de Carvalho Santana

• Advisor: Anderson Marliere Navarro

Abstract

The effectiveness of antiretroviral therapies (ART) increased the life expectancy of HIVinfected patients. However, ART and HIV itself are associated with adipose tissue dysfunction (including mitochondrial dysfunction), which affects systemic metabolism and contributes to the metabolic and morphologic changes observed in HIV-associated lipodystrophy syndrome (HALS). In addition to its storage function, the adipose tissue acts as an endocrine organ. Recently studies have shown the role of brown adipose tissue (BAT) in energy metabolism. Aim: to evaluate subcutaneous adipose tissue and its association with the energetic metabolism of PVHIV with lipodystrophy. Methods: Thirty-three men aged 47.5 ± 6.5 years were enrolled. They were divided into 3 groups: 12 HIV-infected individuals undergoing ART with lipodystrophy (HIV+LIPO+), 10 HIV-infected individuals undergoing ART without lipodystrophy (HIV+), and 11 non-HIV-infected individuals (CTRL). Body composition, resting energy expenditure (REE), glucose and lipid metabolism, and serum adipokine and cytokine concentrations were evaluated. A sample of subcutaneous adipose tissue from the posterior supraclavicular region was collected for the analysis genes related to adipogenesis and adipocyte function (PPAR? and ADIPOQ), biogenesis and mitochondrial respiratory chain (PGC1? and COX4|1), thermogenesis in BAT (UCP1 and DIO2) and microRNA biogenesis, which are important for differentiation and function of brown and white adipocytes (DICER1). The mitochondrial density was evaluated by citrate synthase activity, and mitochondrial metabolism was evaluated by coupled (P), non-phosphorylated (L), and uncoupled (E) states. Results: All PLHIV were clinically stable, with undetectable viral load, and TCD4 of 714 ± 220 cell/ml. There were no differences in age, BMI, and % body fat (% BF) between groups. The CTRL group had higher LDL-C when compared to HIV+, and it tended to have a higher number of people with high-fat percentage (p = 0.08) when compared to the other groups. Markers of glucose metabolism, adipokines, and cytokines were similar between groups. There were no significant differences in REE (p=0,427) and REE/ fat-free mass (FFM) (p=0,154) between HIV+LIPO+, HIV+, and CTRL groups. Mitochondrial metabolism and density were similar between groups. Analysis of molecular markers gene expression showed no changes in expression of PPAR?, ADIPOQ, PGC1?, COX4|1, DIO2, e DICER between groups. Only 8 samples (2 HIV + LIPO +, 3 HIV XIV +, and 3 CTRL) presented UCP1 expression, which was not associated with REE in these people. No associations were found between REE and mitochondrial metabolism, and between REE and the molecular markers analyzed. FFM was a predictor of REE in the HIV+ and CTRL groups, while BF (%) was a predictor of REE in the HIV+LIPO+ group. Conclusion: posterior supraclavicular subcutaneous adipose tissue of PLHIV using ART with lipodystrophy shows no changes in mitochondrial metabolism and density, and in the expression of molecular markers of adipogenesis, adipocyte function, DIO2 and DICER when compared to the adipose tissue of PLHIV without lipodystrophy and non-HIV infected individuals. The expression of the genes analyzed in this tissue is not associated with REE, which was similar between PVHIV, with and without lipodystrophy, and individuals not infected with HIV. (AU)

• FAPESP's process: 16/19155-2 - Influence of brown adipose tissue in energy metabolism of people living with HIV and AIDS
• Grantee: Mariana Palma Guimarães
• Support Opportunities: Scholarships in Brazil - Doctorate