Obesity and Food Addiction Summit

Ernest P. Noble, MD, Ph.D.

Distinguished Professor of Psychiatry and Biobehavioral Sciences and Emeritus Director of the Alcohol Research Center Semel Institute for Neuroscience & Human Behavior at the UCLA School of Medicine

BIOGRAPHY:
Dr. Ernest P. Noble is a distinguished educator, biochemist and clinical psychiatrist. He is considered by many of his colleagues to be one of the world's foremost leaders in the field of alcohol research and is widely recognized for his pioneering research on the effects of alcohol on the brain.

Dr. Noble came to UCLA in 1981 with a distinguished academic and service career. After many years as a faculty member at Stanford University and the University of California at Irvine, Dr. Noble became the Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Washington, DC. Subsequently, he was appointed the Pike Professor of Alcohol Studies at UCLA and Director of the UCLA Alcohol Research Center. There he is directing fundamental studies aimed at understanding the biochemical, physiological and genetic causes of alcoholism. Dr. Noble was also former Vice-President of the National Council on Alcoholism, and former President of the International Commission for the Prevention of Alcoholism and Drug Dependency.

Dr. Noble received his B.S. degree in Chemistry from the University of California at Berkeley. He obtained a Ph.D. in biochemistry from Oregon State University and a Doctor of Medicine degree from Case Western Reserve University followed by medical internship and psychiatric residency training at Stanford University. He has been a Fulbright Scholar at the Sorbonne in Paris, a Guggenheim Fellow at the Centre de Neurochimie in Strasbourg, France, and a Senior Fulbright Scholar at the Max-Planck Institute for Psychiatry in Munich, Germany.

Dr. Noble has over 400 scientific and medical publications to his credit and is a member of numerous editorial boards and scientific and professional societies, and has received many honors for his achievements. In 1990, he and his colleagues were the first to discover the association of the D2 dopamine receptor (DRD2) gene with alcoholism. This study received wide national and international recognition. Subsequently, he has also found the DRD2 gene to be involved in other substance abuse disorders including cocaine, heroin and nicotine addiction and obesity. It is believed that the finding of this reward or pleasure gene opens a window of hope and an opportunity for the prevention and treatment of alcoholism, other drug addictions and obesity.

PERSONAL STATEMENT:

Most of my academic career has been devoted to understanding the biological/genetic basis of alcohol addiction. However, I became interested in food addiction after my colleagues and I identified in 1990 the first gene in alcohol addiction. Specifically, we found the A1 allele (the minor form) of the D2 dopamine receptor (DRD2) gene to be associated with this addiction. This raised the question as to whether the involvement of the DRD2 was unique to alcohol addiction or whether it is common to other addictions. However, before embarking on that search, we wanted to know what the brain characteristics were of subjects who had the DRD2 A1 allele. To do that, we carried out a pharmacological study on the brains of deceased individuals who had or did not have the A1 allele. What we found was that subjects with the A1 allele, regardless of whether they were that of alcoholics or controls, had fewer D2 dopamine receptors than those who lacked this allele.

There is good evidence that the D2 dopamine receptor is an important substrate for the brain dopamine reward or pleasure system. Thus, we reasoned that a paucity of these receptors in A1 allele subjects would render them reward or pleasure deficient. To compensate for this deficiency state, individuals by consuming alcohol, which by releasing brain dopamine and activating their fewer D2 dopamine receptors, would activate their brain dopamine reward or pleasure system. Unfortunately, the continuing use of high amounts of alcohol results in the development of addiction to this drug. It should be noted that this genetic type of alcoholics, that is those with the DRD2 A1 allele, develop the most severe form of alcoholism and are the most difficult to treat.

It is well established that food (particularly carbohydrates), like alcohol, when consumed, increases brain dopamine levels. So by the same analogy as the above, my colleagues and I conducted and published a study in 1994, where we found the DRD2 A1 allele to be also associated with obesity. Thus, these individuals with the A1 allele, having a paucity of their D2 dopamine receptors, have a deficiency in their dopamine brain reward system. To compensate for this state, they consume excessive amounts of food which eventuates in the development of obesity. If these genetic type of obese individuals reduce their food intake (e.g., through dieting), they experience anxiety, depression and other unpleasant feelings. To compensate for these dysphoric states, they restart consuming large amounts of food and fail in their attempts at dieting. It is hypothesized that the genetic type of alcoholics, that is those who carry the DRD2 A1 allele, are the ones that have the greatest difficulties in dieting.

The association of the DRD2 A1 allele with obesity has been replicated and expanded in subsequent studies. Does this finding have utility in the treatment of obesity?

PUBLICATIONS:

Publications of interest by Dr. Noble and colleagues