Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.
Am J Physiol Regul Integr Comp Physiol
; 321(5): R781-R790, 2021 11 01.
Article
em En
| MEDLINE
| ID: mdl-34585616
ABSTRACT
At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age 53 ± 9 yr, body mass index 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Consumo de Bebidas Alcoólicas
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Infecções por HIV
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Sobreviventes de Longo Prazo ao HIV
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Mioblastos Esqueléticos
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Diabetes Mellitus Tipo 2
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Metabolismo Energético
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Músculo Quadríceps
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Mitocôndrias Musculares
Tipo de estudo:
Etiology_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Am J Physiol Regul Integr Comp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article