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Growth Factor Helps Nourish Those Who Can’t Eat

A discovery by University of Wisconsin-Madison scientists may improve the health and speed the recovery of patients who can’t digest and absorb food normally.

Unlike individuals who briefly receive an intravenous glucose solution after surgery, some patients depend completely on a feeding solution to meet all their nutritional needs for weeks or months. This is called total parenteral (meaning “into the vein”) nutrition.

Each year, this technique saves the lives of tens of thousands of adults. They include people with cancer, acute pancreatitis, inflammatory bowel disease, anorexia nervosa, and those who have had major sections of their intestine removed or suffered abdominal gunshot wounds, head injuries, multiple fractures, or severe burns.

Working with rats, nutritional scientist Denise Ney of the College of Agricultural and Life Sciences and colleagues Catherine A. Peterson, Hannah V. Carey and Hui-Chen “Paula” Lo discovered that adding growth factors to the solution helps rats overcome several problems both rats and people develop when they don”t eat food and are maintained with parenteral feeding. The problems include a deterioration of the intestinal wall, loss of weight and muscle mass, and difficulty regulating blood sugar.

“It”s difficult to do this type of research on people, because they tend to be quite sick,” Ney says. “Fortunately, rats respond to total parenteral nutrition much as people do.” A small clinical trial supports some of the group”s findings.

Physicians first used total parenteral nutrition in the 1960s to save premature infants. That solution included amino acids, the building blocks of protein, and glucose, a simple sugar. During the past 30 years, scientists have continued to improve the solution. For example, emulsions of triglycerides – simple fats – were routinely added to the parenteral solution in the 1980s. Ney”s laboratory has spent nearly a decade evaluating which triglycerides are most beneficial in the solution.

“Our understanding of what the body needs for proper parenteral nutrition continues to improve,” says Ney. “Evaluating total parenteral nutrition has become an important way researchers are building a more complete picture of human nutritional requirements.”

Ney”s recent work has focused on the two growth factors: growth hormone and insulin-like growth factor-I. Both are protein hormones the body naturally produces, and both influence how the body uses nutrients for growth and repair.

She is particularly encouraged by the group”s recent finding that insulin-like growth factor I – although not growth hormone – prevents the tissue breakdown of the intestinal wall that occurs in rats that don”t eat and are maintained on parenteral feeding.

“There are finger-like projections in the small intestine that increase the area that absorbs food,” Ney says. “Normally, food passing through the intestine stimulates it to rebuild all of this tissue in rats every few days. When rats don”t eat but receive parenteral feeding, this tissue can atrophy to half its size in just five days.

“The gut is more than an organ to absorb food.” Ney says. “It”s also the body”s largest immune organ. It produces immune cells and serves as a barrier to bacteria and viruses that people swallow. When the intestine atrophies, these microbes can cross the intestinal wall more easily and cause life-threatening infections.”

In related experiments, Ney and Lo found that both growth factors helped prevent weight loss and enhance protein synthesis in rats that had the same abdominal surgery. The researchers compared rats on the control parenteral solution with those given the same solution to which growth hormone, insulin-like growth factor I, or both had been added.

Four days after the surgery the control animals had lost an average of 5 grams, while those receiving either of the growth factors singly had gained 10 grams. The rats that received both growth hormone and insulin-like growth factor I gained an average of 19 grams and made more new tissue protein.

Ney says a recent study in England of 11 critically ill patients supports her findings. That study found that giving patients both growth hormone and insulin-like growth factor I in the solution improved protein synthesis.

“When you”re critically ill, your body doesn”t use nutrients efficiently and often breaks down muscle tissue,” Ney says. “These growth factors help prevent the loss of weight and muscle mass. In other experiments, we found that growth factors do this by causing rats to use the energy available to them in fats and sugars rather than breaking down protein.”

Peterson, a former postdoctoral scientist with Ney, is now at the UW-Stevens Point. Carey is a physiologist at the UW-Madison School of Veterinary Medicine. Lo is a former graduate student in nutritional sciences. The research was supported by grants from the National Institutes of Health and UW-Madison College of Agricultural and Life Sciences. Growth factors used in the research were provided by Genentech, Inc.