Obesity-induced changes in the metabolic and endocrine milieu elicit deficits in neuroplasticity, including increased risk for development of neuropsychiatric disorders such as depressive illness. We previously demonstrated that downregulation of hypothalamic insulin receptors (hypo-IRAS) elicits a phenotype that is consistent with features of the metabolic syndrome (MetS) and that rats with this phenotype exhibit deficits in neuronal plasticity, including depressive-like behaviors such as anhedonia. Since food restriction paradigms effectively inhibit obesity-induced neuroplasticity deficits, the aim of the current study was to determine whether food restriction could reverse obesity-induced anhedonia in hypo-IRAS rats. Compared to hypo-IRAS rats provided ad lib food access, food restriction paradigms that were initiated either prior to increases in body weight or following development of the MetS/obesity phenotype effectively restored sucrose intake in hypo-IRAS rats. Moreover, food restriction paradigms were able to prevent and reverse the changes in the endocrine/metabolic/inflammatory milieu observed in hypo-IRAS, such as increases in plasma leptin and triglyceride levels and increases in pro-inflammatory cytokines such as IL-1α, IL-6 and C-reactive protein (CRP). Collectively, these results demonstrate that obesity-induced anhedonia is a reversible process and identify some potential mechanistic mediators that may be responsible for co-morbid depression in obesity.
Keywords: Depressive illness; Leptin; Metabolic syndrome; Pro-inflammatory cytokines; Triglycerides.
Published by Elsevier Inc.