Discovering the Role of Free Fatty Acids, Essential Modulators of Energy Metabolism

Dole, Vincent
Courtesy of the Rockefeller Archive Center

In the 1950s medical scientists began investigating the relationships between dietary fat and disease. As new methods for separating and analyzing lipids in blood plasma became available, researchers had noticed trace amounts of lipids known as free fatty acids in plasma. Most scientists dismissed them as insignificant, but they captured the curiosity of Vincent Dole (1913-2006). He devised a precise method for determining free fatty acids and measured them in dozens of human subjects, before and after meals with different ratios of fat and carbohydrate. These studies were made possible by his access to patients in the Rockefeller Hospital. The research led him to the discovery that free fatty acids play a vital role in glucose metabolism, a finding that launched major advances in understanding how the human body stores and uses energy.

Dole found that a fatty meal had no effect on the level of free fatty acids in the plasma of his patients. But after a meal high in carbohydrates, or a meal of mixed fat and carbohydrate, free fatty acid levels dropped markedly. An injection of insulin also caused free fatty acids to decrease, whereas an injection of epinephrine, which inhibits insulin secretion, resulted in high levels. In fact, when a person eats carbohydrates, beta cells in the pancreas secrete insulin, which helps convert free fatty acids and glycerol into tryglycerides, which are stored in fat. This process has the effect of removing both free fatty acids and glucose from the blood.

Dole's 1956 report became one of the most highly cited papers ever published in the Journal of Clinical Investigation. As the article was going to press, however, Dole learned that a young researcher at the National Institutes of Health was working on a similar study. That research pointed to another important discovery—the likelihood that free fatty acids served as the main fuel for cardiac muscle. Dole felt that it would be both polite to his junior colleague and helpful to readers to delay publication of his results, and the two articles eventually appeared in the same issue.

Vincent P. Dole received the AB in mathematics from Stanford University in 1934, and the MD from Harvard Medical School in 1939. In 1941, after an internship at Massachusetts General Hospital, he joined the Rockefeller Institute as an assistant in the laboratory of Donald D. Van Slyke. During World War II he joined the Naval Medical Research Unit of the Rockefeller Institute Hospital. After a brief appointment at Harvard University Medical School, he returned to Rockefeller in 1947, and was appointed full member (professor) in 1952. Among many awards and honorary degrees recognizing his work, Dole received the Gairdner Foundation International Award (1972) and the Lasker Award (1988).

Selected Publications

Dole VP. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest, 1956, 35: 150-154

Gordon RS and Cherkes A. Unesterified fatty acid in human blood plasma. J Clin Invest, 1956, 35: 26-212

Further Reading

Hirsch J. One thing leads to another. J Clin Invest, 2004, 114: 1040-1043