Award for General Nutrition In search of the missing link in the regulation of appetite and body weight Sergueï O. Fetissov, M.D., Ph.D.* Digestive System and Nutrition Laboratory (ADEN EA3234), Institute of Biomedical Research, Rouen University, IFR23, Rouen, France Manuscript received and accepted October 2, 2008. How humans and animals regulate appetite and body weight has been explored in numerous studies dealing with genetic, biochemical, environmental, and psychological fac- tors, yet the diseases that primarily affect these physiologic functions remain largely unsolved issues of modern medi- cine. The origin of diseases such as anorexia and bulimia nervosa or binge-eating obesity is often referred to as mul- tifactorial, implying that a combination of the factors cited above should fall into a certain pattern that would trigger disease development. Although this might be true, it does not exclude that there exist biological changes in the organ- ism that may be common and critical for the development of each specific form of eating or metabolic disease. Recent research by me and my colleagues has revealed a new and unexpected biological mechanism that appears as a fundamental part of the homeostatic control of motivated behavior including food intake. In fact, based on clinical and experimental data, we proposed that the regulation of appetite and body weight is under constant control by the immune system by secretion of autoantibodies (autoAbs) directed against neuropeptide or peptide hormones involved in the regulation of energy homeostasis [1,2]. Furthermore, we showed the first evidence that production of such auto- Abs can be influenced by luminal antigens, indicating that these autoAbs may serve as a link between nutrients or gut microflora and brain control of appetite and emotion [3]. I am very grateful that the 12th John M. Kinney Award for General Nutrition was given to recognize the potential importance of this discovery recently reported in Nutrition [3]. The path that led me to identify this new biological mechanism was long and I believe could only become possible due to complementary skills acquired in different laboratories in four countries during my research career. Having graduated as a medical doctor from the Medical Military Academy in St. Petersburg, Russia, and accom- plishing a general surgery internship, I was hesitating if I should start full-time scientific research but meeting with my future Ph.D. supervisor Prof. Michael Ugrumov at the Koltzov Institute of Developmental Biology of the Russian Academy of Science in Moscow helped me to make the choice of selecting science. However, my doctoral research project was closely related to my intention of remaining connected to neurosurgery because it dealt with the trans- plantation of embryonic dopaminergic neurons for eventual application in Parkinson’s disease or for hyperprolactine- mia. In particular, I worked with embryonic arcuate nucleus grafts years before this small hypothalamic structure was recognized as a key brain area responsible for appetite and body weight control and before the emergence of stem cell therapy. From this perspective, it was very useful to become familiar with the arcuate neurons from anatomic and bio- chemical aspects. However, the critical event that turned my subsequent research career toward the study of brain control of appetite and body weight happened in 1994 in France. During my Ph.D. training, in collaboration with the Institute of Neuroscience directed by Prof. André Calas at Pierre and Marie Curie University in Paris, I met with Prof. Stelianos Nicolaïdis. He was at the time head of the laboratory at the College de France in Paris, applying several behavioral, metabolic, and neurochemical approaches to study the brain control of appetite and body weight and formulating an ischymetric hypothesis of food intake control. Being a former neurosurgeon, he appreciated my surgical skills and invited me to participate in a postdoctoral training to study the effects of transplantation of embryonic arcuate neurons in obese Zucker rats. During 2 y of work in his laboratory, we found that the arcuate neurons grafted from the lean Zucker rats in the hypothalamus of obese rats resulted in a significant reduction of body weight gain and an improve- ment of insulin resistance. We also found that the obese * Corresponding author. Tel.: +33-0-2-3514-8455; fax: +33-0-2- 3514-8226. E-mail address: Serguei.Fetissov@univ-rouen.fr (S. O. Fetissov). Nutrition 25 (2009) 252–254 www.nutritionjrnl.com 0899-9007/09/$ – see front matter © 2009 Published by Elsevier Inc. doi:10.1016/j.nut.2008.10.002