Altered skeletal muscle fatty acid handling is associated with the degree of insulin resistance in overweight and obese humans.
Diabetologia
; 59(12): 2686-2696, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27627982
ABSTRACT
INTRODUCTION/HYPOTHESIS:
Disturbances in skeletal muscle fatty acid (FA) handling may contribute to the development and progression of whole-body insulin resistance (IR). In this study, we compared fasting and postprandial skeletal muscle FA handling in individuals with varying degrees of IR.METHODS:
Seventy-four overweight/obese participants (62 men) were divided into two groups based on the HOMA-IR median (3.35). Fasting and postprandial skeletal muscle FA handling were determined by combining the forearm muscle balance technique with stable isotopes. [2H2]palmitate was infused i.v. to label VLDL-triacylglycerol (VLDL-TAG) and NEFA in the circulation, whereas [U-13C]palmitate was incorporated in a high-saturated FA mixed-meal labelling chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid content, fractional synthetic rate (FSR) and the transcriptional regulation of FA metabolism.RESULTS:
Postprandial forearm muscle VLDL-TAG extraction was elevated in the high-IR vs the mild-IR group (AUC0-4h 0.57 ± 0.32 vs -0.43 ± 0.38 nmol [100 ml tissue]-1 min-1, respectively, p = 0.045). Although no differences in skeletal muscle TAG, diacylglycerol, NEFA content and FSR were present between groups, the high-IR group showed increased saturation of the intramuscular NEFA pool (p = 0.039). This was accompanied by lower muscle GPAT1 (also known as GPAM) expression (p = 0.050). CONCLUSIONS/INTERPRETATION:
Participants with high-IR demonstrated increased postprandial skeletal muscle VLDL-TAG extraction and higher saturation of the intramuscular NEFA pool vs individuals with mild-IR. These data support the involvement of disturbances in skeletal muscle FA handling in the progression of whole-body IR.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
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Sobrepeso
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Ácidos Graxos
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Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article