Expression of neural markers of gustatory signaling are differentially altered by continuous and intermittent feeding patterns

Highlights

• Short-term, continuous or limited access to dietary fat increase average daily kilocaloric intake, without significantly increasing body weight.

• Short-term, continuous access to HFD and limited, daily access to dietary fat increase lingual expression of the CD36, the proposed fat taste receptor.

• Continuous, but not daily or intermittent access to a high fat meal alters markers of homeostatic eating in the mediobasal hypothalamus.

• Limited, intermittent access to dietary fat selectively altered the expression of markers of hedonic eating.

• Differential effects of meal patterns on gustatory neurocircuitry may regulate the overconsumption of fat and lead to obesity.

Abstract

Food intake patterns are regulated by signals from the gustatory neural circuit, a complex neural network that begins at the tongue and continues to homeostatic and hedonic brain regions involved in eating behavior. The goal of the current study was to investigate the short-term effects of continuous access to a high fat diet (HFD) versus limited access to dietary fat on the gustatory neural circuit. Male Sprague-Dawley rats were fed a chow diet, a HFD (56% kcal from fat), or provided limited, daily (2 h/day) or limited, intermittent (2 h/day, 3 times/week) access to vegetable shortening for 2 weeks. Real time PCR was used to determine mRNA expression of markers of fat sensing/signaling (e.g. CD36) on the circumvallate papillae, markers of homeostatic eating in the mediobasal hypothalamus (MBH) and markers of hedonic eating in the nucleus accumbens (NAc). Continuous HFD increased mRNA levels of lingual CD36 and serotonin signaling, altered markers of homeostatic and hedonic eating. Limited, intermittent access to dietary fat selectively altered the expression of genes associated with the regulation of dopamine signaling. Overall, these data suggest that short-term, continuous access to HFD leads to altered fat taste and decreased expression of markers of homeostatic and hedonic eating. Limited, intermittent access, or binge-like, consumption of dietary fat led to an overall increase in markers of hedonic eating, without altering expression of lingual fat sensors or homeostatic eating. These data suggest that there are differential effects of meal patterns on gustatory neurocircuitry which may regulate the overconsumption of fat and lead to obesity.

Introduction

The overconsumption of highly palatable, high fat foods has been linked to an increase in the prevalence of obesity and multiple studies propose that the timing or pattern in which these energy dense meals are consumed may contribute to weight gain and increase metabolic risks [1], [2], [3]. Eating patterns (e.g. how much, how often, macronutrient composition) are regulated by signals from the gustatory neural circuit, a complex neural network that begins at the tongue and continues to homeostatic and hedonic brain regions involved in feeding and reward. Taste is an important modulator of fat intake and fat preference and initiates a cascade of neural events that leads to changes in food intake [4], [5], [6], [7], [8]. Recent studies have demonstrated that expression levels of lingual fat sensors are related to obesity in clinical populations and animal models [7], [8], [9], [10], [11], [12]. Therefore, patterns of fat intake may affect the expression of lingual fat sensors, which in turn, may alter downstream neural targets and play a role in the preference for and consumption of dietary fat.

CD36 is a lingual fat sensor that regulates fat intake, is expressed primarily on the circumvallate papillae (CV) of the tongue and is considered the fat taste receptor [9], [13], [14], [15], [16], [17], [18], [19]. Studies investigating the role of lingual CD36 on fat intake and preference in models that differ in their susceptibility to develop obesity suggest that lingual CD36 mRNA expression is increased by short-term fat intake in obesity-prone rats, but that taste preference thresholds for linoleic acid are not altered, suggesting desensitization of the taste signal [13], [15], [18]. In another study, chronic consumption of a high fat diet (HFD) reduced CD36 mRNA expression levels compared to chow fed rats [20]. Overall, these studies suggest that dietary fat consumption leads to a dysregulation of fat sensing from the tongue and suggests that this dysregulation may alter the gustatory neural circuitry.

Lingual fat signaling via CD36 involves the regulation of serotonin (5-HT) in taste receptor cells and activation of gustatory afferent nerves [9]. Gustatory afferent nerves project to neural regions associated with eating behaviors, which are regulated by both homeostatic and hedonic mechanisms [21], [22], [23]. Studies suggest that a binge-like pattern of eating and obesity are consequences of overconsuming high fat, highly palatable foods and are due to a shift from homeostatic eating to hedonic, reward-driven eating [24], [25]. The goal of the current study was to investigate the short-term effects of multiple fat intake patterns on the expression of lingual markers of fat sensing and neural markers of homeostatic and hedonic eating.