We are what we eat

Throughout different species, food intake and energy storage are controlled as an intricate system of ‘checks and balances’, which is technically defined “homeostatic system”. As food is ingested, cues from smell and taste information are integrated in the brain with neural and hormonal signals from the rest of the body. These signals report the state of nutritional and energy load, such as the distension of stomach walls, the nutrient levels in the intestine, the fat and glucose levels in the blood, etc. The brain coordinates these information like an orchestra director and, as a consequence, the drive to eat decreases ensuring that the amount consumed in a single meal does not exceed what the body can safely handle.

In the human body, the internal elements of this homeostatic system have not changed in the last 50 years, while a dramatic increase of overweight and obese individuals has been registered. Remarkable changes in the same period occurred in the sensory side of the control process. Social habits related to eating have changed. Grazing, snacking, eating on the go became common thank tothe enormous variety and availability of food, the quite low cost of many food supplies, their enhanced attractive properties (pleasant-tasting, smell, texture, colour), and their constant promotion and advertisement. These external factors cause an hyper exposure to sensory cues able to overwhelm and short-circuit the body’s normal regulatory system, thus contributing, together with less exercise, to the occurring “obesity epidemic”.

How can we tweak these elements playing out of control? Re-educating our eating habits is certainly the first step, but strengthening the brain responsiveness to the normal “internal” cues, can give us the best opportunity to combat obesity. Although the perception of fullness clearly involves higher cerebral centres, the primary brain regions that elaborate signals from the periphery are the hypothalamus and the brainstem. A number of molecules, produced by our body, represent the alphabet of such dialogue. Some of them derive from the fat tissue itself, such as leptin, which communicates the adiposity state. Others arise from multiple sites of the gastrointestinal system and represent the core of the “gut-brain axis”. One emerging element of this axis is a lipid compound called oleoylethanolamide (OEA).

The role played by OEA in the complexity of energy control has been the focus of my research at the Department of Physiology and Pharmacology of Sapienza University of Rome, Italy.

OEA is produced by the first tract of the small intestine and it mainly comes from oleic acid, a compound particularly abundant in olive oil. In the intestine, OEA interacts with the intracellular PPAR-alpha receptors to trigger a domino-like cascade ending in the hypothalamus and the brainstem through the involvement of sensory nerve fibres raising from the intestine. High levels of OEA can reduce appetite, produce weight loss and lower blood cholesterol and triglyceride levels. Interestingly, this same molecule is able to strengthen the memory of emotional events, possibly linking the high caloric and hedonic value of fat-rich food to the formation of a stable imprint in our brain, which, when excessive, might lead to the food cravings and compulsive eating. I found that the OEA signal appears out of control in patients who suffered from anorexia and binge eating disorders, thus, supporting the hypothesis of its role in the onset of such diseases.

My ongoing research, in collaboration with colleagues from the University of California, Irvine and the Italian Institute of Technology, is currently exploring the nature of the mark left by OEA in the brain by investigating the neuronal circuits activated by this signal and the following responses sent to the body. Surprisingly, my preliminary results suggest that these circuits may include those known to regulate our social interactions, such as social bonds, and our reactivity to social stress. This can possibly contribute to explain why obesity and eating disorders have such a close link with psychological/behavioural problems and mostly support the notion that they are diseases caused by chemical imbalances not the mere results of a fragile will incapable of self-control.

What we eat is more than simple fuel intake, it encodes a series of information into the brain that form the basis of our possible future choices. We are not just input/output machines. We are adaptive beings, whose habits are influenced by external stimuli as well as by our own internal chemicals. Understanding how such complex network works, through this kind of research, might help in developing both drug therapies and behavioural strategies that can redirect eating habits and energy metabolism toward a normal pattern.

Gaetani S, Fu J, Cassano T, Dipasquale P, Romano A, Righetti L, Cianci S, Laconca L, Giannini E, Scaccianoce S, Mairesse J, Cuomo V, and Piomelli D. The fat-induced satiety factor OEA suppresses feeding through central release of oxytocin. J Neurosci, 2010