Effect of metabolic syndrome on anxiety in mice

Abstract

Metabolic syndrome is a combination of obesity, dyslipidemia, insulin resistance and hypertension. Clinical evidence indicated the coexistence of metabolic syndrome and depression. However, relatively few studies have been attempted to determine the pathogenesis of metabolic syndrome-associated anxiety. In the present study, the role of metabolic syndrome in the development of anxiety and the role of neurotransmitters in metabolic syndrome-associated anxiety were evaluated in Swiss albino mice. A high-fat and high-carbohydrate diet was used to develop the metabolic syndrome in mice while monitoring elevated fasting blood glucose, hyperlipidaemia and hypertension. Anxiety levels were measured using elevated plus maze and marble burying test with corresponding determination of serum corticosterone levels. The role of γ-aminobutyric acid and serotonin in metabolic syndrome-associated anxiety were also evaluated. The high-fat and high-carbohydrate fed animals developed metabolic syndrome, characterized by significant high fasting blood glucose and insulin resistance compared to controls. These animals also had significant increase in body weight and waist circumference, low-density lipoprotein and triglyceride levels, reduced high-density lipoprotein content and high blood pressure. Both metabolic syndrome and water avoidance-anxiety groups spent significantly lower time and showed fewer entries into the open arm of elevated plus maze. They also buried more marbles, thus showing clear signs of anxiety when compared to controls. The corticosterone level in metabolic syndrome and anxiety-induced animals were higher than controls. GABA agonists showed a dose-dependent reduction in metabolic syndrome-associated anxiety as revealed by more time spent on the open arm of plus maze with a corresponding decrease in plasma corticosterone levels. Metabolic syndrome animals spontaneously developed anxiety-like behaviour. GABA agonists partially reversed the metabolic syndrome-associated anxiety, suggesting a role for GABAergic pathway.