Jules Hirsch, whose clinical investigations into body weight regulation helped establish the biological underpinnings of obesity — including that a person’s weight is in part determined by the body’s own predisposition — died on July 23 in Englewood, N.J. He was 88.
His death was confirmed by a nephew, Norman Silber.
Dr. Hirsch had a long career at the Rockefeller University in New York, including as physician in chief at Rockefeller University Hospital from 1992 to 1996. An advocate of patient-oriented research — in which a doctor investigates the mechanism of disease by studying his own patients — he specialized in studies of metabolism, focusing in particular on why some people get fat and others don’t.
That research was crucial to a shift in approach in obesity studies. Through the middle of the 20th century, fat cells, known as adipose tissue, were considered to be inert storage units for fat that the body burned for energy.
That view reinforced the popular perception that obese people were to blame for their own condition — that they must be lazy or gluttonous or lacking in will power.
Over the years, Dr. Hirsch and others showed that to the contrary, many people are biologically predisposed to be heavy, and that even when they manage to lose weight, biological processes work against their being able to keep it off.
Dr. Hirsch demonstrated that fat cells came in different sizes, and that weight loss reduced the size but not the number of such cells.
The discovery provided evidence that fat cells, far from being inert depots, communicate with the brain, and that the brain keeps track of how much fat is in the body and to some extent regulates it.
In 1994, researchers at Rockefeller isolated the communicating agent, a hormone called leptin, which, when secreted from fat cells, tells the brain how big those cells are.
The scientists also determined that the brain used leptin to maintain a base level of body fat.
“Dr. Hirsch’s work was seminal in demonstrating that there is this flexibility of fat cell size, which provided an anatomic basis for a signal between the body’s adipose tissue and the brain,” Dr. Rudolph L. Leibel, a research partner of Dr. Hirsch’s, said in an interview.
Dr. Leibel was among those responsible for the discovery of leptin.
For 10 years, beginning in the mid-1980s, he and Dr. Hirsch studied 41 volunteers — some obese, some lean — while regulating their weights with liquid formulas.
The study’s findings, released to acclaim in 1995, showed that the body worked against attempts to lose — or gain — weight: When the body slims down, its metabolism slows down and its muscles burn fewer calories with the same effort; when the body beefs up, it burns calories more briskly.