Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity.
Am J Physiol Endocrinol Metab
; 316(2): E168-E177, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30576243
ABSTRACT
Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have been suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In this study, we hypothesized that mitochondrial complex II dysfunction plays a role in impaired insulin sensitivity in visceral adipose tissue of subjects with obesity. We obtained subcutaneous and visceral adipose tissue biopsies from 43 subjects with obesity (body mass index ≥ 30 kg/m2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) ( P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat ( P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat ( P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity ( P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Processamento de Proteína Pós-Traducional
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Complexo II de Transporte de Elétrons
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Gordura Intra-Abdominal
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Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Assunto da revista:
ENDOCRINOLOGIA
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FISIOLOGIA
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METABOLISMO
Ano de publicação:
2019
Tipo de documento:
Article