The Neurobiology of Obesity

Obesity is an energy balance regulation dysfunction that leads to an excessive fat deposition, which increases the risk for cardiovascular, respiratory, and metabolic diseases, in particular when such deposition occurs within the abdominal cavity. The high prevalence of obesity and its costly co-morbidities has significantly contributed to intensify efforts to understand obesity, which is currently at the forefront of biochemical, biomolecular, and neurobiological research. We now confront the tremendous challenge of preventing obesity and developing effective treatments. In the last 15 years, research has generated many important discoveries, including those of adipose tissue-derived hormones such as leptin and adiponectin, those of the gastrointestinal tract hormones such as ghrelin, and the determination of numerous central and peripheral circuitries involved in energy balance regulation. The neurobiology of obesity represents a rapidly growing research field that has proved to be essential in the understanding of the etiology of obesity. The brain plays a major role in energy balance regulation as it exerts controls on both food intake and energy expenditure (Figure 1). Three brain entities are particularly important in these controls, namely the hypothalamus, the dorsal vagal complex, and the reward system, which are inter-related structures capable of controlling energy intake as well as thermogenesis. Brain systems controlling energy intake and energy expenditure have been divided into anabolic and catabolic systems, each system comprising different types of neurons capable of controlling energy intake as well as energy expenditure. These neurons release various molecules that include neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, the endocannabinoids, α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated transcript, corticotropin-releasing factor, thyrotropin-releasing hormone, and serotonin. These neurosystems are modulated by short- and long-term signals that report on the status of the energy stores and energy fluxes. Whereas leptin and insulin are recognized as the main long-term signals, the gastrointestinal hormones ghrelin, peptide tyrosine-tyrosine, cholecystokinin, and glucagon-like peptide 1 are known as short-term signals that inform about the nutritional status. The way an organism regulates energy balance is in large part a function of its genes and the environment. One energy expenditure component, which is perhaps not so important in human energetics but which is undoubtedly relevant in laboratory rodents used by most neurobiologists of obesity, is brown adipose tissue thermogenesis, the activity of which depends on factors activating the sympathetic nervous system. The extraordinary thermogenic power of brown adipose tissue is attributable to uncoupling protein 1, a mitochondrial protein uniquely found in brown adipose tissue. The regulation of energy stores. NPY, neuropeptide Y; AgRP, agouti-related peptide; MCH, melanin-concentrating hormone; DVC, dorsal vagal complex; αMSH, alpha-melanocyte-stimulating hormone; CART, cocaine- and amphetamine-regulated transcript; CRF, corticotropin-releasing factor; TRH, thyrotropin-releasing hormone; SNS, sympathetic nervous system; GI, gastrointestinal; BAT, brown adipose tissue; UCP1, uncoupling protein 1. It is within the mission of the Merck Frosst/CIHR Research Chair in Obesity to provide continuing education about the best possible knowledge on obesity to scientists, physicians, health professionals, as well as to the public at large, regarding the causes, complications, treatment, and prevention of obesity. In this regard, the purpose of the annual symposium is to summarize evidence regarding important topics related to obesity and to propose novel obesity research directions. Since its creation in 1997, the Merck Frosst/CIHR Research Chair in Obesity has held six international symposia devoted entirely to obesity research. The first symposium of the series, entitled “The Uncoupling Proteins and Obesity,” was held in 1998 (1). The second symposium, which was organized the following year, was oriented toward “The New Biology of Adipose Tissue” (2). In 2000, the third symposium was entitled “The Ponderostat: From Behavior to Neural Substrates” (3) and focused on the mechanisms whereby energy balance is regulated. The fourth symposium, organized in November 2002 and entitled “Complications of Obesity: The Inflammatory Link,” summarized the latest most important findings on the mechanisms underlying the link between obesity and its complications such as diabetes and cardiovascular diseases (4). In 2003, the fifth symposium brought a comprehensive view on the “Role of Gene Regulation in Obesity and its Complications” (5) and, specifically, on the regulation of peroxisome proliferator-activated receptors, prostaglandin C-1, Forkhead transcription factor-1, and silent information regulator 2. In 2004, the sixth symposium focused on the understanding of “The Endocannabinoid System and its Role in Energy Homeostasis and Abdominal Obesity Management” (6). Given the originality and importance of the research currently in progress on the neurobiology system aimed at unraveling the mechanisms whereby energy homeostasis is achieved, better understanding of obesity, and determining therapeutic targets, an advisory committee on the symposium series recommended to the Chair to organize the present symposium on that important topic. The Scientific Program Committee for this symposium, which was chaired by D. Richard (Canada), included K. Sharkey (Canada), W. Colmers (Canada), and A. Ferguson (Canada). P. Boisvert was in charge of the symposium logistics. The present proceedings recapitulate the highlights of the seventh symposium of the Merck Frosst/CIHR Research Chair in Obesity, which was entitled “The Neurobiology of Obesity.” The symposium was held November 4–5, 2005, at Auberge Saint-Antoine in Québec City, Canada. The first of the three one-half-day sessions, chaired by W. Colmers, was aimed at presenting overviews of “The Regulation of Energy Balance.” The second session was chaired by A. Ferguson and was dedicated to the “Circuitries Involved in Energy Balance Regulation.” Finally, K. Sharkey chaired the third session, entitled “Targets for Drugs,” on the peripheral and central mechanisms controlling food intake and energy balance. In closing, our gratitude goes to all of the invited experts, who not only presented authoritative and stimulating presentations but also participated with enthusiasm and competence in the lively discussion periods of the meeting. We thank K. Sharkey, A. Ferguson, and W. Colmers, who very skillfully chaired the meeting sessions and provided direction during the invigorating discussion periods. K. Sharkey, A. Ferguson, W. Colmers, and D. Richard hold a New Emerging Team research grant from the Canadian Institutes of Health Research. This supplement of Obesity was edited by D. Richard and P. Boisvert. We also acknowledge the contribution of the Centre de Recherche de l'Hôpital Laval affiliated to Université Laval, as well as Desjardins Sécurité Financière for their support. This symposium was supported by an unrestricted grant from Merck Frosst Canada Limited.

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