Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back

REVIEW published: 24 April 2018 doi: 10.3389/fnins.2018.00271 Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back Roberto Coccurello 1,2* and Mauro Maccarrone 2,3* 1 Department of Biomedical Sciences, Institute of Cell Biology and Neurobiology, National Research Council, Rome, Italy, Laboratory of Neurochemistry of Lipids, European Center for Brain Research (CERC), IRRCS Santa Lucia Foundation, Rome, Italy, 3 Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy 2 Edited by: Heike Vogel, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Germany Reviewed by: Jorge Mendoza, UPR3212 Institut des Neurosciences Cellulaires et Intégratives (INCI), France Giovanni Laviola, Istituto Superiore di Sanità, Italy *Correspondence: Roberto Coccurello Mauro Maccarrone Specialty section: This article was submitted to Neuroenergetics, Nutrition and Brain Health, a section of the journal Frontiers in Neuroscience Received: 29 November 2017 Accepted: 09 April 2018 Published: 24 April 2018 Citation: Coccurello R and Maccarrone M (2018) Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back. Front. Neurosci. 12:271. doi: 10.3389/fnins.2018.00271 Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to identify potential factors responsible for the derangement of homeostatic eating toward hedonic eating and addiction-like feeding behavior. Here, we examined recent literature on “old” and “new” players accountable for reward-induced overeating and possible liability to eating addiction. Thus, the role of midbrain dopamine is positioned at the intersection between selected hormonal signals involved in food reward information processing (namely, leptin, ghrelin, and insulin), and lipid-derived neural mediators such as endocannabinoids. The impact of high fat palatable food and dietary lipids on endocannabinoid formation is reviewed in its pathogenetic potential for the derangement of feeding homeostasis. Next, endocannabinoid signaling that regulates synaptic plasticity is discussed as a key mechanism acting both at hypothalamic and mesolimbic circuits, and affecting both dopamine function and interplay between leptin and ghrelin signaling. Outside the canonical hypothalamic feeding circuits involved in energy homeostasis and the notion of “feeding center,” we focused on lateral hypothalamus as neural substrate able to confront food-associated homeostatic information with food salience, motivation to eat, reward-seeking, and development of compulsive eating. Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin neurons to integrate endocrine signals with food reinforcement and hedonic eating. In addition, the role played by different stressors in the reinstatement of preference for palatable food and food-seeking behavior is also considered in the light of endocannabinoid production, activation of orexin receptors and disinhibition of dopamine neurons. Finally, type-1 cannabinoid receptor-dependent Frontiers in Neuroscience | www.frontiersin.org 1 April 2018 | Volume 12 | Article 271 Coccurello and Maccarrone Endocannabinoid and Dopamine Signaling in Food Reward inhibition of GABA-ergic release and relapse to reward-associated stimuli is linked to ghrelin and orexin signaling in the lateral hypothalamus-ventral tegmental area-nucleus accumbens network to highlight its pathological potential for food addiction-like behavior. Keywords: hedonic food, dopamine, endocannabinoids, leptin, ghrelin, orexin, insulin, lateral hypothalamus FRAMING FATTY ACIDS AND ADIPOCYTE-DERIVED LEPTIN SIGNALING WITHIN THE BRAIN REWARD SYSTEM high levels of circulating leptin obese individuals cannot rely on leptin signaling neither to reduce appetite nor to increase energy expenditure. This condition is well-known as “leptin resistance” and develops gradually as function of body adiposity, from residual sensitivity to exogenous leptin to almost total suppression of brain leptin sensitivity (Lin et al., 2000). The excessive eating of dietary fat not only dysregulates the homeostatic control of feeding behavior and body weight, but has also a great importance in the derangement of the brain hedonic system. Overeating is a maladaptive behavior that is triggered and sustained by the escalation of easily accessible palatable or hyperpalatable (e.g., high fat, sugar-rich, and often salty diet) food, that exacerbates energy intake and vulnerability to hedonic experience. Leptin function and signaling link the regulation of energy homeostasis to the incentive and reward value of food and nutrients. Indeed, leptin-mediated effects are not limited to feeding circuits but extend over involving hedonic, cognitive and stress neuronal circuits (Morrison, 2009; Farr et al., 2015). The key point to understand the two faces of energy homeostasis (i.e., energy loss or satiation and energy intake or hunger) is to look at the intricate puzzle where nutritional status and reward value of food coexist. It is recognized that starvation or food restriction significantly enhances motivation for rewarding stimuli, including craving for palatable food and drugs of abuse (Carr, 2007). Leptin can exert a dual action by reducing food intake and also motivation to attain rewards (Figlewicz et al., 2001, 2004, 2006; Carr, 2007; Shen et al., 2016). Reinforcing properties of both palatable food (Hommel et al., 2006) and addictive substances (Shen et al., 2016) are encoded by dopamine (DA) transmission within the mesocorticolimbic network, encompassing the projection neurons of the ventral tegmental area (VTA) in the midbrain that relays DA-ergic signals to the ventral striatum (nucleus accumbens, NAc), amygdala and prefrontal cortex (PFC). Although DA shows to be a neural communication system shared by food and drug seeking, a perfect isomorphism between these two processes would be an oversimplification. Here, we will assume that drugs and palatable foods are potent reinforcers that disrupt the brain mechanisms underlying synaptic plasticity and energy homeostasis, that show common vulnerabilities and pathophysiological aspects (Volkow et al., 2011b). Thus, the highly conserved mesocorticolimbic DA circuit plays a fundamental role in the assignment of motivational/rewarding value to biologically relevant stimuli (Kelley and Berridge, 2002). (...truncated)