Pioglitazone rescues high-fat diet-induced depression-like phenotypes and hippocampal astrocytic deficits in mice

This is the authors' abstract. We don't add key points for this paper.

The prevalence of diabetes is rapidly increasing worldwide and is highly associated with the incidence of depression. Pioglitazone, a Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is widely used for treating patients with type 2 diabetes. However, whether pioglitazone alleviates metabolic disorder-related depression and astrocytic deficits remains unclear. Here we showed that 12 weeks of high-fat diet (HFD) feeding (from 8- to 20-week-old) induced not only obesity and insulin resistance, but also depression-like behaviors in mice. Astrocytic activation, a sign closely associated with depression, was also evident in the ventral hippocampus. Four weeks of pioglitazone (10 or 20 mg/kg, daily, from 20- to 24-week-old) treatment alleviated the HFD-induced glucose-metabolic dysfunctions, upregulation of ventral hippocampal GFAP, reduction of the total process lengths and the number of branch points of the ventral hippocampal CA1 GFAP-immunoreactive astrocytes and depressive phenotypes but had no effect on anxiety-like behaviors or hippocampus-related learning and memory in mice. These findings suggest that pioglitazone could be a potential therapeutic agent for metabolic disorders and associated depression.