Hedonic Eating: Sex Differences and Characterization of Orexin Activation and Signaling

Abstract

Palatable taste can stimulate appetite in the absence of hunger, and individual differences in hedonic eating may be critical to overeating. Women are more prone to obesity and binge eating than men, which warrants comparisons of hedonic versus physiological consumption and the underlying neural substrates in both sexes. The current study examined palatable (high-sugar) food consumption in male and female rats under physiological hunger and satiety, and the role of the neuropeptide orexin/hypocretin (ORX). Across multiple tests, females consistently consumed similar amounts of palatable food regardless of whether they were hungry or sated prior to testing. In contrast, males typically adjusted their consumption according to their hunger/satiety state. This difference was specific to palatable food consumption, as both sexes ate standard chow according to their hunger state. ORX is important in food motivation and reward behaviors. Thus, to begin to determine the neuronal mechanisms of hedonic eating, we examined activation and signaling of ORX neurons. We systematically characterized Fos induction patterns of ORX neurons across the entire rostrocaudal extent of the lateral hypothalamus and found that they were activated by food and by fasting in both sexes. Then, we showed that systemic blockade of ORX receptor 1 signaling with SB-334867 decreased palatable food consumption in hungry and sated rats of both sexes. These results demonstrate sex differences in hedonic eating; increased susceptibility in females to overeat palatable food regardless of hunger state, and that ORX is a critical neuropeptide mechanism of hedonic eating in both sexes.

Keywords: consumption; hedonic; orexin; overeating; palatability; sex differences.

Figure 1

Image acquisition and analysis A. Representation of the sampling regions is shown on a modified rat brain atlas template (level 29, Swanson, 2004). Images were taken in four sampling regions arranged in respect to the fornix (fx): perifornical area (pf), located dorsomedial to the fornix, dorsolateral (dl), ventromedial (vm), and ventrolateral (vl). B. Image shows representative types of labeled neurons. Arrows point to a representative of each type of labeled neuron: single-labeled Fos (gray), single-labeled ORX (brown), and double-labeled ORX and Fos. The scale bar (B) = 50 pm

Figure 2

Consumption during testing session A. Consumption of TD shown in grams (mean±SEM) B. Consumption of TD expressed as a percentage of rat’s body weight (mean±SEM). * indicates Male Ad Lib different (p < 0.005) from each other group (n=8 per group).

Figure 3

Images of Fos induction in ORX neurons. Images show induction of Fos (gray) in ORX neurons (brown) in ad libitum-fed male groups that were either tested without food (A) or given food (B), fasted males groups that were either tested without food (C) or given food (D), ad libitum-fed females groups that were either tested without food (E) and with food (F), and fasted female groups that were either tested without food (G) and with food (H). All images are from perifornical area. The scale bar (G) = 100 μm

Figure 4

Fos induction in ORX neurons. Graphs show the percentage of total ORX neurons that were labeled with Fos in male and female Ad Lib and Deprived groups that either received food or no food during testing (mean ± SEM). * indicates a difference (p < 0.05) between Ad Lib and Deprived and between Food and No Food conditions (N=7–8/group; N=29 for each Ad Lib, Deprived, Food, and NoFood conditions).

Figure 5

Consumption tests with TD (Test 1) and chow (Test 2) A. Consumption of TD expressed as a percentage of rat’s body weight (mean ± SEM). B. Consumption of regular chow expressed as a percentage of rat’s body weight (mean ± SEM). indicates a difference (p < 0.0001) between Deprived and Ad lib (n=16 per condition; n=8 per sex).

Figure 6

Consumption tests after ORX-R1 antagonist blockade. Graph shows consumption after rats received SB or Veh in a within-subjects design across two counterbalanced tests (Test 3 & 4). * indicates a difference (p< 0.005) between Vehicle and SB (n=15–16 per condition, n=7–8 per sex), # indicates a difference between Ad Lib and Deprived males (p = 0.002 n=7–8 per group).

Figure 7

Consumption tests with TD and chow. Graph shows consumption across two tests (Test 5 & 6) with TD and regular rat chow in a within-subjects design (the order of tests was counterbalanced). * indicates a difference between TD and Chow for Ad Lib males (p = 0.038; n=8) and females (p = 0.001 n=8), # indicates a difference in TD consumption between Ad Lib and Deprived males (p = 0.001 n=8 per group).