Abstract
BackgroundInsulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.MethodsMale Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.ResultsIn addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.ConclusionsThese results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.
Highlights
Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue
The objective of the present study was to determine whether a selective β3-AR agonist could prevent alterations in the profile of skeletal muscle and adipose tissue lipids induced with the consumption of the cafeteria diet, previously reported to induce weight gain and hyperinsulinemia [22,23]
Our results indicate that a β3-AR agonist prevents some cafeteria diet-induced alterations of the fatty acid profile of lipids in skeletal muscle and adipose tissue
Summary
Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Dietary fatty acids are known to influence the composition of stored triacylglycerol (TAG) and membrane phospholipids (PL) in adipose tissue [1]. The modifications of fatty acid concentrations and composition in tissue lipids induced by a high fat diet has been associated with alterations in lipid metabolism and insulin sensitivity [5,6]. Intramyocellular TAG could represent only a marker of insulin resistance whereas intracellular accumulation of long chain acyl-coenzyme A, ceramide or diacylglycerol (DAG) were reported to directly alter the insulin action [14]
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