Obesidad

Appetite and Hedonism: Gut H o r m o n e s a n d th e Brain
Katherine A. Simpson, MB, ChB, MRCP, Stephen R. Bloom, MA, MD, DSc, FRCPath, FRCP, FMedSci*
KEYWORDS  Appetite  Food  Gut hormones  Hypothalamus  Brainstem  Reward

The ability to maintain adequate food intake is fundamental to survival. At times of famine, the drive to maintain energy intake can be so powerful that humansresort to extreme behavior to survive. For example, it was such a situation that drove the Nantucket crew onboard the Essex whaleship in 1820 to break all taboos and resort to cannibalism in their lifeboat after the ship was sunk by a sperm whale.1 In contrast, when homeostatic mechanisms controlling food intake are poorly adapted to the unique modern environment of plenty, both excess energy intakeand reduced exercise result in widespread obesity. Globally, the World Health Organization (WHO) estimates that more than 1 billion adults and more than 42 million children younger than 5 years are overweight.2,3 Obesity is associated with diabetes mellitus, hyperlipidemia, hypertension, cardiovascular disease, and certain forms of cancer.4 Evolutionarily, it is advantageous that the consumption offood is associated with feelings of reward, and at times of famine the stored energy is utilized efficiently when needed. However, in today’s society, such reward-seeking behavior and the constant availability of highly palatable food is a major factor for the increased incidence of obesity. The control of food intake is complex and consists of neural and hormonal signals between the gut andcentral nervous system (CNS). In addition, signals relating to energy reserves such as adipose tissue, as well as genetic predisposition to obesity, are involved. The brain is responsible for interpreting the signals from the periphery and increasing or decreasing food intake depending on energy reserves and the wanting of food. Even before eating, gut hormones are released and begin the process ofmeal termination and feelings of satiation. Gut hormones act within key brain areas

Section of Investigative Medicine, Imperial College London, Commonwealth Building, Du Cane Road, London, W12 0NN, UK * Corresponding author. E-mail address: s.bloom@imperial.ac.uk Endocrinol Metab Clin N Am 39 (2010) 729–743 doi:10.1016/j.ecl.2010.08.001 0889-8529/10/$ – see front matter Ó 2010 Elsevier Inc. Allrights reserved. endo.theclinics.com

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such as the hypothalamus and brainstem, which contain intricate neuronal networks and connections to other parts of the brain that are involved with reward and desirability. As such, there is a basic need for centers within the brain to be able to respond at times of hunger or satiation and adjust food intake accordingly. However,reward centers can override this mechanism beyond homeostatic need when faced with desirable and palatable food.
HYPOTHALAMUS

The hypothalamus consists of several important nuclei that are involved in appetite control and energy homeostasis: the arcuate nucleus (ARCN), paraventricular nucleus (PVN), ventromedial nucleus (VMN), dorsomedial nucleus (DMN), and lateral hypothalamic area (LHA).These nuclei receive neuronal connections from other parts of the brain, such as the brain stem (which receives gut vagal afferents) and reward centers (Fig. 1). In addition, certain hormones such as insulin and leptin are able to exert a direct effect via the circulation and access the ARCN via a saturable process across the blood-brain barrier (BBB). Some investigators have postulated that there isalso an incomplete BBB at the median eminence of the hypothalamus and area postrema of the brainstem, perhaps allowing other peptides to act directly on important CNS centers that control food intake.
Arcuate Nucleus

The ARCN contains many neuronal populations involved in food intake. Of these, the best characterized are the neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons, which...