RESUMO
Obesity is frequently associated with the development of type 2 diabetes which is firstly characterized by a defect in the response of key metabolic tissues to insulin (insulin resistance). The imbalance in fatty composition of the diet, a low-grade inflammatory state have been described to be involved in the initiation or the amplification of the molecular events involved in this process. The concept of a specific nutritional intervention has emerged as a promising tool against metabolic disorders associated with obesity. In this context, many investigations were conducted to evaluate the potential beneficial impacts of n−3 polyunsaturated fatty acids (n−3 PUFA). The aim of the present review was to summarize the current knowledge about the role of docosahexanoic acid (DHA, 22:6n−3) and eicosapentanoic acid (EPA, 20:5n−3) on key metabolic organs. Only studies aiming to understand the mechanism of actions were selected. The analysis of randomized clinical trial about n−3 PUFA was not considered here. The effects of n−3 PUFA were analyzed in the adipose tissue, the liver, skeletal muscle and the pancreas in the context of obesity and lipid oversupply. Furthermore, in line with recent findings about the role of the modulation of gut microbiota in obesity-related disorders, we summarized the recent findings about the possible link between n−3 PUFA and change in microbiota composition
Assuntos
Humanos , Ácidos Graxos Insaturados/farmacocinética , Diabetes Mellitus/prevenção & controle , Insulinas/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Substâncias Protetoras/farmacocinética , Obesidade/fisiopatologia , Intestinos/microbiologiaRESUMO
Obesity is frequently associated with the development of type 2 diabetes which is firstly characterized by a defect in the response of key metabolic tissues to insulin (insulin resistance). The imbalance in fatty composition of the diet, a low-grade inflammatory state have been described to be involved in the initiation or the amplification of the molecular events involved in this process. The concept of a specific nutritional intervention has emerged as a promising tool against metabolic disorders associated with obesity. In this context, many investigations were conducted to evaluate the potential beneficial impacts of n-3 polyunsaturated fatty acids (n-3 PUFA). The aim of the present review was to summarize the current knowledge about the role of docosahexanoic acid (DHA, 22:6n-3) and eicosapentanoic acid (EPA, 20:5n-3) on key metabolic organs. Only studies aiming to understand the mechanism of actions were selected. The analysis of randomized clinical trial about n-3 PUFA was not considered here. The effects of n-3 PUFA were analyzed in the adipose tissue, the liver, skeletal muscle and the pancreas in the context of obesity and lipid oversupply. Furthermore, in line with recent findings about the role of the modulation of gut microbiota in obesity-related disorders, we summarized the recent findings about the possible link between n-3 PUFA and change in microbiota composition.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Insulina/metabolismo , Humanos , Ilhotas Pancreáticas/metabolismo , Músculo Esquelético/metabolismoRESUMO
Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia. We studied six healthy subjects after an overnight fast and during an induced 5-hour period of hyperglycemia with hyperinsulinemia. Muscle fatty acid oxidation was calculated using stable isotope methodology combined with blood sampling from the femoral artery and vein of one leg. Muscle functional CPT-1 activity was assessed by concurrently infusing an LCFA tracer and a CPT-independent medium-chain fatty acid tracer. Muscle biopsies were obtained from the vastus lateralis after the periods of fasting and hyperglycemia with hyperinsulinemia. Hyperglycemia with hyperinsulinemia decreased LCFA oxidation, but had no effect on LCFA uptake or medium-chain fatty acid oxidation across the leg. Malonyl-CoA concentration significantly increased from 0.13 +/- 0.01 to 0.35 +/- 0.07 nmol/g during hyperglycemia with hyperinsulinemia. We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle.