High-fat diet-induced obesity and insulin resistance are characterized by differential beta oscillatory signaling of the limbic cortico-basal ganglia loop

Lukas Maurer,Joachim Spranger,Andrea A Kühn,Christoph Van Riesen,Jens K Haumesser,Hui Tang,Jennifer Altschüler

doi:10.1038/s41598-017-15872-x

Abstract

The concept of brain circuit disorders has been proposed for a variety of neuropsychiatric diseases, characterized by pathological disturbances of neuronal networks including changes in oscillatory signaling of re-entrant cortico-subcortical loops in the basal ganglia system. Parts of this circuitry play a pivotal role in energy homeostasis. We therefore investigated whether high-fat diet (HFD) induced obesity is associated with changes in oscillatory signaling in the limbic cortico-basal ganglia loop. We performed multi-site in-vivo electrophysiological recordings of local field potentials within this network under urethane anesthesia in adult rats after 4 weeks of HFD feeding compared to age-matched controls. Recordings were performed at baseline and during systemic glucose challenge. Our analysis demonstrates increased oscillatory beta power in the nucleus accumbens (NAC) associated with decreased beta coherence between cortex and NAC in animals fed a HFD. Spontaneous beta oscillatory power strongly correlated with endocrine markers of obesity. The glucose challenge increased beta oscillations in control animals but not in animals receiving the HFD. Furthermore direct intracerebroventricular insulin injection increased beta oscillations in the NAC. The present study provides evidence for aberrant oscillatory signaling in the limbic cortico-basal ganglia loop that might contribute to the dysfunctional information processing in obesity.

Highlights

The prevalence of obesity and type 2 diabetes (T2DM) has reached epidemic proportions worldwide[1]
We demonstrate that high fat diet (HFD) induced obesity is characterized by an increase of beta oscillatory power in the limbic cortico-basal ganglia loop that is most pronounced in the nucleus accumbens (NAC) and accompanied by a decreased coherence in the beta frequency band between the NAC and the medial prefrontal cortex (mPFC)
The standard i.p. glucose tolerance test (GTT) was conducted during the electrophysiological recordings under urethane anesthesia revealing a significantly higher area under the curve (AUC) glucose level for the HFD group compared to controls

Summary

Introduction

The prevalence of obesity and type 2 diabetes (T2DM) has reached epidemic proportions worldwide[1]. The limbic cortico-basal ganglia loop plays a central role in the brains reward circuitry that is responsible for the processing of reward related aspects of food consumption and it is intricately interconnected with hypothalamic midbrain areas that regulate the organism’s homeostatic functions[5]. While a number of these aspects like impaired dopaminergic neurotransmission[14] or neuronal injury due to hypothalamic inflammation[15] have been addressed in the context of obesity, the question of whether aberrant network activity occurs in the involved neuronal circuits has not been clarified To address this important question we aimed to characterize information processing in the limbic cortico-basal ganglia loop by simultaneous multi-site local field potential (LFP) recordings. NAC beta activity is highly correlated to diet-induced elevations of insulin and leptin levels at baseline while showing a differential group-dependent response towards a systemic glucose challenge

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