Abstract
Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver.
Highlights
Stages of insulin resistance are characterized by increased insulin secretion from pancreatic β-cells for maintaining glucose homeostasis under overfeeding conditions [1]
As we previously described [23], the high-fat high-sucrose (HFHS) diet significantly increased the body weight, the perigonadal white adipose tissue weight, the fasting plasma insulin (FI) concentration and the Homeostatic Assessment Model of Insulin Resistance (HOMA-IR) value compared to the standard (STD) diet
Individual fish oil (FO) and grape seed extract (GSE) supplementations did not attenuate either hyperinsulinemia or increased HOMA-IR induced by the HFHS diet compared to the STD diet
Summary
Stages of insulin resistance are characterized by increased insulin secretion from pancreatic β-cells for maintaining glucose homeostasis under overfeeding conditions [1]. Insulin resistance is a common feature in metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), and is related to disturbances in lipid metabolism [2] Several studies in both rodents and humans support the hypothesis that the aberrant accumulation of bioactive lipids such as diacylglycerol (DAG) and ceramide in the liver is a key step in the pathogenesis and progression of insulin resistance and NAFLD [3]. Mitochondrial fatty acid oxidation is promoted to prevent lipid accumulation in the liver under fat overload [11] This fact might lead to increased reactive oxygen species production and, as a consequence, oxidative damage to lipids, proteins and DNA [11]
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