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1. Obesity Dyshomeostasis Linked to Ghrelin, Leptin and Dopamine Responses to Sustained Stress

   • David F. Marks

   Independent scholar

   Burghardt et al. (2012) present interesting evidence that leptin serves a regulator function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The authors suggest that the capacity for leptin to influence stress-induced dopaminergic function is potentially important for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

   It is generally agreed that food intake is regulated by two complementary drives: the homeostatic and hedonic pathways (Lutter and Nestler, 2009). The homeostatic pathway controls energy balance by increasing the motivation to eat following depletion of energy stores. Hedonic or reward-based regulation can override the homeostatic pathway during periods of relative energy abundance by increasing the desire to consume foods that are highly palatable.

   The paper by Burghart et al. (2012) is exclusively concerned with leptin. Another hormone involved in both homeostatic and hedonic regulation of food intake is ghrelin, the only mammalian peptide hormone able to increase food intake. Interestingly, ghrelin also responds to emotional arousal and stress (Labarthe, Fiquet, Hassouna, Zizzari et al., 2015; Mueller et al., 2015). During chronic stress, increased ghrelin secretion induces emotional eating by acting at the level of the hedonic/reward system. As ghrelin has anxiolytic action in response to stress, this adaptive response may contribute to control excessive anxiety and prevent depression (LaBarthe et al., 2015). In obesity, studies have shown a reduced ability to mobilize ghrelin in response to stress or central ghrelin resistance at the level of the hedonic/reward system which may explain the inability to cope with anxiety and increased susceptibility to depression. Reciprocally, studies have shown that people with depression have increased susceptibility to obesity and eating disorders (Marks, 2015).

   Traditionally, the control of feeding has been associated with the hypothalamus (Kelley, Baldo, Pratt & Will, 2005). Circulating factors in the blood modulate the activity of energy sensing neurons in the arcuate nucleus, that modulate food-directed behaviours via their activation of outputs from lateral hypothalamic regions to thalamo- cortical systems, central autonomic effectors, and motor pattern generators. There is a convergence of inputs from amygdala, prefrontal cortex, and nucleus accumbens shell that allow direct modulation of feeding behaviours based upon cognitive and affective signaling. These avenues of influence on feeding control provide the entry point for a Circle of Discontent (Marks, 2015). When the environmental conditions are: (A) obesogenic, due to the ready availability of highly palatable high- energy foods; (B) stressful, due to the presence of stigma, depression and anxiety; and (C) engendering body dissatisfaction, due to the omnipresent socio-cultural thin-ideal, we have all the ingredients necessary for obesity formation. It is proposed that the cognitive and affective processes of the Circle of Discontent over-ride the homeostasis system for regulating feeding and energy-homeostasis breaks down (Marks, 2015). The capacity of both leptin and ghrelin to influence stress- induced dopaminergic function such as mood, substance-use disorders, eating disorders, and obesity warrants further investigation.

   Burghardt PR, Love TM, Stohler CS, Hodgkinson C, Shen PH, Enoch MA, Goldman D, Zubieta JK. (2012) Leptin regulates dopamine responses to sustained stress in humans. The Journal of Neuroscience 32:15369-76.

   Kenny P J (2010) Reward mechanisms in obesity: new insights and future directions. Neuron 69: 664 - 679.

   Labarthe A, Fiquet O, Hassouna R, Zizzari P et al. (2015). Ghrelin- derived peptides: a link between appetite/reward, GH axis, and psychiatric disorders? Neurological and Psychiatric Disorders in Endocrine Diseases, 71.

   Lutter m and nestler ej (2009) Homeostatic and hedonic signals interact in the regulation of food intake. Journal of Nutrition 139: 629- 632.

   Marks D F (2015) Homeostatic theory of obesity Health Psychology Open 1(2).

   Mueller T D, Nogueiras R, Andermann M L, Andrews Z B et al. (2015) Ghrelin. Molecular Metabolism 4: 437-460.

   Conflict of Interest:

   None declared

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   Published February 29, 2016