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  • Review Article
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Neurobiology of food intake in health and disease

Nature Reviews Neuroscience volume 15, pages 367–378 (2014)Cite this article

Subjects

Key Points

  • The energy homeostasis system effectively ensures stability of body fat stores under usual conditions by processing humoral inputs related to both total body energy stores and current nutrient availability and transducing them into neuronal signals that powerfully influence the perception of satiety on the one hand and of food reward on the other.

  • During conditions of negative energy balance (for example, starvation or a calorically restricted diet), homeostatic responses are engaged to promote increased food intake by reducing the satiating while enhancing the rewarding properties of food.

  • Two well-studied leptin-sensing neuronal subpopulations involved in feeding are those that co-express neuropeptide Y, agouti-related protein (AGRP; an antagonist of melanocortin signalling) and GABA, and those that express pro-opiomelanocortin (POMC).

  • Optogenetic and pharmacogenetic (designer receptors exclusively activated by a designer drug) strategies demonstrate that AGRP neuronal activation is sufficient to rapidly and potently stimulate food and increase the motivation to work for food.

  • Conversely, stimulation and inhibition of POMC neurons using either optogenetics or DREADDs in mice reduces and increases food intake, respectively through the melanocortin receptor 4.

  • Neurocircuits exist that are normally inhibited, but when activated in response to emergent or stressful stimuli, can override the homeostatic control of energy balance.

  • In response to the lack of either immediately available fuel (such as hypoglycaemia) or the amount of stored fuel (leptin deficiency), the brain triggers an overlapping set of responses that drive increased food intake.

  • During conditions of stress, trauma and illness, a neurocircuit involving calcitonin gene-related peptide-containing neurons in the parabrachial nucleus is activated that functions as an 'off' switch' for feeding.

  • Improved knowledge of how these emergency-activated circuits interact with the energy homeostasis system is fundamental for understanding the control of food intake and may bear on the pathogenesis of disorders at both ends of the body weight spectrum.

Abstract

Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. However, this homeostatic system can be overridden by the activation of 'emergency response circuits' that mediate feeding responses to emergent or stressful stimuli. Inhibition of these circuits is therefore permissive for normal energy homeostasis to occur, and their chronic activation can cause profound, even life-threatening, changes in body fat mass. This Review highlights how the interplay between homeostatic and emergency feeding circuits influences the biologically defended level of body weight under physiological and pathophysiological conditions.

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Figure 1: CNS regulation of energy homeostasis.
Figure 2: Integration of long-term homeostatic and short-term satiety signals.
Figure 3: Integration of homeostatic and reward-related inputs.
Figure 4: Neurocircuits involved in the homeostatic regulation of feeding.
Figure 5: Activation of emergency neurocircuits that inhibit feeding.

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Acknowledgements

This work was supported by a US National Institute of Diabetes and Digestive and Kidney Diseases Grant to M.W.S (DK090320, DK083042, and DK052989) and G.J.M. (DK089053), the US National Institutes of Health (NIH) funded Nutrition Obesity Research Center (DK035816) and Diabetes Research Center (DK17047) at the University of Washington and a NIH Diabetes and Metabolism training Grant (F32 DK097859; T32 DK0007247).

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  1. Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, 98109, Washington, USA

    Gregory J. Morton, Thomas H. Meek & Michael W. Schwartz

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PowerPoint slides

Glossary

Energy homeostasis

The biological process by which the body maintains body fat stores by balancing energy intake with energy expenditure over time.

Anorexia

A disorder that is characterized by a reduction in energy intake and accompanied weight loss.

Adiposity negative feedback signals

Hormones that circulate in direct proportion to body fat and convey the state of total energy stores to the CNS.

Satiety

The state of feeling full to the point of satisfaction after the consumption of food.

Neuropeptide

A small protein-like molecule that is used by neurons to communicate with each other, often in a paracrine manner.

Optogenetics

A technique that uses light to control the activity of specific neurons in living tissue.

DREADD

(Designer receptor exclusively activated by a designer drug). G protein-coupled receptors that are modified for activation by binding to inert small molecules that are used to non-invasively control neuronal signalling.

Neurotransmitters

Chemical messengers that are released by the end of a nerve fibre, causing an impulse to be passed from once cell to another.

Leptin resistance

A state in which the body is no longer responsive to the anorexic effect of exogenous leptin.

Conditioned taste aversion

(CTA). A learned response of an animal to avoid repeated ingestion of certain foods that cause nausea or sickness.

Cachexia

A condition that is characterized by anorexia, weight loss and disproportionate wasting of muscle and adipose tissue.

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Morton, G., Meek, T. & Schwartz, M. Neurobiology of food intake in health and disease. Nat Rev Neurosci 15, 367–378 (2014). https://doi.org/10.1038/nrn3745

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