Dyshomeostasis in human feeding

In an environment that promotes widespread body dissatisfaction, angst and depression, homeostatic feedback loops are producing excessive consumption of unhealthy processed foods that over a protracted period causes obesity in large numbers of vulnerable people. Multiple clinical studies in different areas of medicine demonstrate the primary role of homeostasis in healthy functioning and the consequences of dyshomeostasis. Homeostasis can be overloaded or overridden with too strong a flow of inputs or outputs that disrupt its normal functioning: ‘The homeostatic behaviour of inflow controllers breaks down when there are large uncontrolled inflows, whereas outflow controllers lose their homeostatic behaviour in the presence of large uncontrolled outflows’ (Drengstig et al., 2012). Homeostasis can be disrupted anywhere, and perturbations will inevitably occur in normal functioning (Richards, 1960).

There are many examples of dyshomeostasis in clinical medicine. Well-known to psychologists, Hans Selye reported that a persistent environmental stressor (e.g. temperature extremes), together with an associated homeostatic hormonal response, leads to tissue injury that he termed a ‘disease of adaptation’ (Selye, 1946). Intestinal homeostasis breaks down in inflammatory bowel disease (Maloy and Powrie, 2011) and in the microbial ecology of dental plaque causing dental disease (Marsh, 1994). This form of dyshomeostasis can result from local infection and inflammation and give rise to complications that affect the nervous and endocrine systems (Maynard et al., 2012). An altered balance between the two major enteric bacterial phyla, the Bacteroidetes and the Firmicutes, has been associated with clinical conditions. Within the microbiota of the gut, obesity has been associated with a decreased presence of bacteroidetes and an increased presence of actinobacteria (Ley, 2010; Turnbaugh and Gordon, 2009). Kamalov et al. (2010) proposed a dyshomeostasis theory of congestive heart failure. Craddock et al. (2012) suggested a zinc dyshomeostasis hypothesis of Alzheimer’s disease.

Homeostasis regulation within the endocrinal and central nervous systems has been associated with feeding control. Cortical areas conveying sensory and behavioural influences on feeding provide inputs to the nucleus accumbens (NAc) and the lateral hypothalamic area (LHA) is the site of homeostatic and circadian influences (Saper et al., 2002). Hormones such as leptin circulate in proportion to body fat mass, enter the brain and act on neurocircuits that govern food intake (Morton et al., 2006). Through direct and indirect actions, it is hypothesized that leptin diminishes the perception of food reward while enhancing the response to satiety signals generated during food consumption that inhibit feeding and lead to meal termination.

Another important hormone is ghrelin which is the only mammalian peptide hormone able to increase food intake. Interestingly, ghrelin also responds to emotional arousal and stress (Labarthe et al., 2014; Müller 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., 2014). 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 (Figure 1). Reciprocally, studies have shown that people with depression have increased susceptibility to obesity and eating disorders (Marks, 2015).

Figure 1. Model of hedonic/reward response to ghrelin after chronic stress in relation to anxiety and depression. Reproduced from Labarthe et al. (2014).

During chronic stress, increased ghrelin secretion induces emotional eating as hedonic reward. Ghrelin has anxiolytic actions in response to stress; this adaptive response helps to control excessive anxiety and prevent depression. In obesity, a lower ability to mobilize ghrelin in response to stress or central ghrelin resistance at the level of the hedonic/reward system may explain the inability to cope with anxiety and increased susceptibility to depression. Reciprocally, people suffering from depressed show increased susceptibility to obesity or eating disorders (due to an altered hedonic/reward response). Elevated ghrelin may also contribute to alcohol/drug craving as higher ghrelin levels correlate with greater alcohol craving.

In addition to leptin and ghrelin, other lipid messengers that modulate feeding by sending messages from the gut to the brain have been identified. For example, oleoylethanolamine has been associated with control of the reward value of food in the brain (Lo Verme et al., 2005; Tellez et al., 2013). Mice fed a high-fat diet had abnormally low levels of oleoylethanolamine in their intestines and did not release as much dopamine compared to mice on low-fat diets. Thus, alterations in gastrointestinal physiology induced by excess dietary fat may be one factor responsible for excessive eating in the obese (Tellez et al., 2013).

Extracted from Marks (2016)

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