The New York Obesity Nutrition Research Center

CO-DIRECTOR, F. Xavier Pi-Sunyer, M.D

Dr. Pi-Sunyer became Director of the NYONRC on July 1, 1988, after a full national search process. At that time, Dr. Van Itallie retired as Director. Dr. Pi-Sunyer is an internationally recognized scientist who has been working in the area of obesity for over forty years. Dr. Pi-Sunyer is Chief of the Division of Endocrinology, Diabetes, and Nutrition at St. Luke’s/Roosevelt Hospital Center and Professor of Medicine at Columbia University. He has been a member of the NIH Nutrition Study Section and of Study Section --, as well as an ad hoc reviewer for a large number of other NIH Study Sections.

Dr. Pi-Sunyer has served on numerous task forces for the NIH, the American Diabetes Association, the American Heart Association, and the Obesity Society. He headed the NIH Task Force that wrote the Guidelines for the Prevention and Treatment of Obesity that were published by the government in 1997. He has served as one of 13 experts chosen for the USDA/HHS Dietary Guidelines Advisory Committee in 2005 and again in 2010. He was on the FDA Science Forum, the top advisory board to the FDA Commissioner. He has served on 3 Institute of Medicine task forces. Dr. Pi-Sunyer served as the editor-in-chief of the journal Obesity Research and is now on its editorial board. He is now on the NHLBI Combined Guidelines Committee.

Dr. Pi-Sunyer’s research over the years has been multi faceted, but all of it has been focused on aspects of nutrition as they relate to carbohydrate and lipid metabolism, and as they relate to the pathophysiology of obesity and diabetes. He has conducted his research along with a number of outstanding collaborators.

His initial work involved the effect of inflammatory pancreatitis on insulin release. He studied in man the effect of autonomic denervation on counter regulatory metabolic and hormonal responses during intracellular hypoglycemia. He studies islet cell transplantation: cell culture and preservation for eventual transplants; localization of transplantation sites; post transplantation innervation, insulin and glucagon secretion

Dr. Pi-Sunyer investigated the metabolic effects during starvation of animals whose adipose tissue he enriched with odd numbered medium chain fatty acids, and showed beneficial effects on glucose,and insulin, and prevention of lipolysis and ketonemia.

He focused on the gut peptide regulation of food intake in human subjects. Utilizing a computerized eating monitor, he followed cumulative intake curves of eating, measuring quantity, duration, and rate of eating. He found CCK 8, bombesin, and glucagon all to be inhibitory of food intake, in both lean and obese subjects. He pursued mechanistic studies of the inhibitory effect of food intake by CC K 8 in man, showing that the partial pre meal filling of the stomach is important in enhancing the food satiating effect, that gastric emptying is slowed; that it increases gastric pressure.

Thermogenesis has been a strong interest. Dr. Pi-Sunyer showed that obese persons have a higher resting metabolic rate than leans, and that obesity is associated with a diminished thermic effect of food. He studied the relationship of the reduction of RMR with weight loss in relation to the changes of different body compartments. He also measured the resting metabolic rate of obese women of black and white origin, he found, doing careful body composition determinations, that black women have consistently lower resting metabolic rate for a given lean body mass. This lower thermogenesis may be part of the explanation for the much greater prevalence of obesity in this group.

He documented that men who are overweight but muscular, without excess fat, have risk factors for lipids, diabetes, and blood pressure which are normal, as compared to a group of similarly overweight men who are overfat. Thus, it is the fatness, and not the weight per se, that determines disease risk.

Dr. Pi-Sunyer compared high protein and balanced macronutrient weight loss diets with regard to body compositional loss, showing that there is no difference in body protein loss on the two diets, but only an initial difference in water loss, which equalizes in the long term. This was the first prolonged study in humans showing no special advantage of a high protein over a balanced macronutrient diet during weight loss.

In long term metabolic balance studies of the effect of exercise on food intake and body composition in obese and lean human volunteers, he showed clearly that lean and obese persons respond differently. Lean persons compensate quickly and accurately while obese persons do not and thereby lose weight.

In adipocyte metabolism experiments, he focused on the role of fatty acid synthesis in the control of insulin mediated glucose utilization. He also investigated the differences in glucose metabolism by fat cells from differing adipose tissue depots. He showed that white fat from different depots differ with regard to nutrient utilization.

Studying women with upper and lower body obesity, Dr. Pi-Sunyer found that upper (or central) body obesity was related to increased cardiovascular and diabetes health risks in both black and white women, but the effects were more serious in white than in black women, with higher blood pressure, higher lipids, and greater insulin resistance. He then showed that for a given amount of obesity, black women have less VAT than do white women. Thus, the lesser health risks in black women relate to their smaller deposits of VAT at a given level of obesity. The role of VAT accumulation on fatty acid and glycerol turnover rates was studied using a pancreatic euglycemic clamp in non diabetic, premenopausal women with a wide range of VAT. In both races, VAT accumulation was associated with systemic resistance to the anti lipolytic effect of insulin, helping to explain their health risks. He also documented that visceral obesity in humans is associated with resistance to the anti lipolytic effect of insulin in vivo and in vitro, and that abdominal adipocytes are less sensitive to the anti lipolytic effect of insulin than gluteal adipocytes.

He showed that while the body mass index is still a predictor of mortality in people over 70 years of age, the base of the Ushaped curves is fairly wide, so that acceptable body mass index can be 28 to 30 before mortality risk is increased. Also, he demonstrated that fat loss is associated with lower mortality whereas lean body mass loss is associated with a higher mortality. This is the first study of its kind showing a differential effect of weight loss depending on whether predominantly lean body mass or fat is lost. In addition, he found that the intra uterine environment influences on birth weight have an enduring impact on adult height but could document no impact on adult relative weight.

Recently, Dr. Pi-Sunyer has become interested in the regulation of leptin secretion in humans. He has found synergistic effects of feeding and dexamethasone on serum leptin levels. Dexamethasone has no independent effect on serum leptin in the absence of food intake. Rather, dexamethasone appears to potentiate the food induced increase in serum leptin. This synergism may be mediated by insulin and/or other factors associated with food ingestion.

Dr. Pi-Sunyer is a founding member and serves on the Steering Committee of the Diabetes Prevention Program. He also is co-Chair and a member of the Executive Committee of the LookAhead Trial. These are two NIH-sponsored behavior modification programs to see the outcome of cardiovascular disease in patients with impaired glucose tolerance and type 2 diabetes.

In summary, Dr. Pi-Sunyer has a long history of clinical research in obesity, including significant translational research quickly adapted to the patient. He has maintained a clinical presence as Chief of Endocrinology, Diabetes and Nutrition at his hospital. He has also been a leader in education of physicians and students in the prevention and treatment of obesity. He has also led the NYORC since 1988. He is well qualified to direct the Center.

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