Where fat is located on the body and how its location affects your health

The Centers for Disease Control and Prevention estimate that obesity costs the United States at least $117 billion annually. 60 percent of Americans over age 30 are overweight; one-third are obese.

Obesity is a major risk factor for diabetes—a disease that accounts for one-fourth of all Medicare expenditures. Current projections estimate that one in three children born in 2000 will develop diabetes. Obesity also increases the risk of high blood pressure, coronary artery disease, stroke, cancer and osteoarthritis.

The expanding statistics bring a sense of urgency to the obesity research of endocrinologist Michael Jensen, M.D. Dr. Jensen's group is an arm of Mayo's Endocrinology, Diabetes, Metabolism and Nutrition research, which studies the chemical and physical processes that convert food into energy. Dr. Jensen is internationally recognized for his exceptional contributions to furthering the understanding of weight regulation, fat storage, fat distribution and the effects of weight gain on health. His body of publications includes more than 119 peer-reviewed journal articles, 16 books and book chapters, and more than 70 abstracts.

Location, Location, Location

One of Dr. Jensen's main interests is the mechanisms that control where fat is located on the body and how its location affects your health.

When it comes to fat storage, humans can be divided into two major body types: apples—who store fat around the waist, and pears—who store it on the hips and thighs. Studies have shown that those of us who fall into the apple crate are more likely to develop obesity-related health problems. Dr. Jensen's work has led scientists in a new direction.

The previously well-traveled research path concentrated on studying intra-abdominal fat because high levels of fatty acids in the bloodstream correlate with the large amounts of intra-abdominal fat present in 'apples.'

"There was a very nice idea that intra-abdominal fat causes harm by flooding your body with extra fatty acids," says Dr. Jensen. "However, through a series of studies done over many years, we were able to prove that it is fat under the skin in the upper body that is the real source of extra fat in the bloodstream."

The discovery refocused obesity research efforts from intra-abdominal fat to subcutaneous fat.

( J R Soc Med. 2002, 95 Suppl. 42:3-7)

"We've had a series of papers over the last decade that has systematically chipped away at this," says Dr. Jensen. "We feel our studies have given us a sound understanding of the physiological roles of intra-abdominal and subcutaneous fat. Now that we have the big picture we are ready to dig deeper with cell and molecular biology studies. We want to uncover what's different about the genes and cells of subcutaneous fat, understand the mechanisms that regulate it, and discover ways to remove it."

Fat cells are shown before measurement (A); with diameters outlined (B); and numbered to ensure correct cell identification (C).

Dr. Jensen studies the effects of acute and chronic overeating on fat storage and fat distribution.

"By feeding people very special meals, we can follow fat right to the fat cells. We feed some a normal meal, and others a fatty one to see if that changes where they store their fat. When we find out where it goes, we make sophisticated measurements that help us understand why it went there."

A great help in this regard is Mayo's metabolic kitchen—one of the services provided by Mayo Clinic's outstanding General Clinical Research Center (GCRC).

"Many of our studies depend on being able to provide participants with precisely calculated and weighed diets," says Dr. Jensen. "We can rely on the metabolic kitchen to do that accurately."

Dr. Jensen is a member of both the Lipid Core Group and the Nutrition Core Group. Both groups benefit from the team of specially trained nurses, technical and support staff to closely monitor participants in their human studies at the GCRC. The center provides an environment that maximizes patient safety, protocol quality, and interaction between scientists and clinicians. It also serves as an excellent training environment for clinical investigators.

Why is Bad Fat Bad?

"I want to understand the mechanisms in fat metabolism that control whether or not fat accumulation is harmful to health," says Dr. Jensen. "To do that we must first identify the difference between the good fat that goes to one location and the bad fat that goes to another."

The ultimate goal is to understand the mechanisms well enough to be able to modify them—with the focus on improving the patient's health rather than appearance.

"90 percent of type 2 diabetes is caused from bad fats and they also cause much of the high cholesterol problems," says Dr. Jensen. "My goal is to decrease the health risks of those people who have difficulty losing weight by having them store a kind of fat that does not cause harm."

Tracking Fat Molecules

Dr. Jensen's lab has a unique idea—and the ability to conduct studies on how fat cells cause harm by infiltrating muscle. He hypothesizes that fat build-up in muscle interferes with its ability to take up and burn sugar, which causes blood sugar levels to rise and, if it happens in great enough amounts, leads to malfunction of the pancreas and diabetes.

Using sophisticated mass spectrometry, Dr. Jensen tracks fat molecules from the blood stream to the internal structures of the cell. By tracking plasma free fatty acids (FFA) during exercise, he has shown that FFA availability can increase two to four times with moderate exercise. Fatty acids are a major fuel source for humans both at rest and during exercise. FFAs are the major circulating lipid fuel.

In addition, he has found that when a muscle contracts it can stimulate triglyceride metabolism inside the muscle cell—a finding that suggests fat metabolism is regulated from within the cell. He has also found that endurance training and dietary factors can influence the way fat is metabolized.

Another Mayo study on gender differences concluded that women released 40 percent more FFA into the circulation for a given energy expenditure. The finding may have implications in treating metabolic complications of obesity.

NEAT Discovery

Are you one of those people who teeter on the thin edge of envy when you watch a lean person tuck into a calorie-loaded dessert?

In a study published in Science (1999: 283, 212-214), Dr. Jensen collaborated with endocrinologist James Levine, M.D., and Norman Eberhardt, Ph.D., an endocrinology researcher and a member of the Department of Biochemistry and Molecular Biology to uncover a physiological reason for why some people don't seem to gain weight, even when they overeat. They called it NEAT — non-exercise activity thermogenesis. You may know it as "fidgeting," a word coined by science journalists when it was widely reported in the media. It means that some people resist gaining weight by automatically triggering an impulse to increase movement when they overeat.

Dr. Jensen's chief excitement regarding this project is that it helped launch a successful research career for Dr. Levine, who was a post-doctoral fellow in Dr. Jensen's lab when the studies began.

"Jim has since set up a NIH-funded research program to further understand human energy requirements and its relevance to obesity," says Dr. Jensen. "He is widely recognized in the scientific community for his innovative approach to obesity research."

Dr. Levine is also continuing this line of research in a project funded by the Minnesota Partnership for Biotechnology and Medical Genomics—a partnership that teams Mayo Clinic and University of Minnesota scientists.

While the phenomenon of weight resistance by some individuals after overfeeding was known, the team designed the study because its mechanism remained a mystery. For the first two weeks, the metabolic kitchen prepared meals to stabilize the volunteers' weight. That was followed by eight weeks of overfeeding by 1000 calories per day. What set the study apart was the creative use of sophisticated laboratory equipment to track exactly what happened to the excess food.

"We measured every possible component of energy expenditure with great precision," explains Dr. Jensen. "So we were able to tell how energy was stored as fat, how much energy had been expended and, to some extent, how each component had been expended."

Weight gains varied from two to almost 16 pounds. The investigators were surprised by the finding regarding weight resistance.

"We thought it would be some passive way of wasting extra calories—something that did not involve movement," says Dr. Jensen. "But the thing that changed most in people who didn't gain weight was the increase in their energy expenditure. We found that some people have a huge capacity to resist weight gain by unconsciously moving around."

The finding increases the understanding of the mechanisms of weight regulation. Dr. Jensen is excited that his bench research may translate into practical treatments for his patients.

"Since NEAT describes a behavior, there may be some things that we can do to help people change behavior and facilitate their ability to maintain a healthy weight," says Dr. Jensen. "We are considering ways to cue people to behave in a way that simulates NEAT."

The Importance of State-of-the-Art Technology

Immature fat cells, called preadipocytes, from human subcutaneous adipose tissue during growth phase.

Dr. Jensen is one of the world's leading experts on regulation of lipid metabolism and how—when altered—it contributes to obesity. He has steadily worked to produce outstanding results and credits Mayo for generously supporting his research in many ways, including the purchase of equipment. However, because the technology changes so quickly, research can lag without access to the latest equipment.

In point of fact, Mayo does have the equipment that Dr. Jensen needs. However, it is housed in Mayo's Mass Spectrometry Lab where it's tied up in other projects. The machine needs to be to be pulled apart and reconstructed to accommodate Dr. Jensen's studies—a difficult and time-consuming complication.

"We have some promising preliminary results from our current equipment and we have a collection of muscle biopsy samples in the freezer," says Dr. Jensen. "It would be wonderful to have an instrument that would allow us to accelerate our pace—and with half the work that we're now doing."

Mayo initially supported Dr. Jensen by providing the funding necessary to establish a laboratory as he launched his scientific career. Now that he is well-funded with extramural grants, Mayo continues support by supplying space, equipment, core facilities and secretarial support. Such support illustrates Mayo's recognition of its most valuable resource—enthusiastic staff like Dr. Jensen who put the patient first.

"If I didn't need sleep I would come in earlier and if I didn't have a family I'd stay later," admits Dr. Jensen. "It's incredibly exciting work and thrilling to think that my research helps people understand their weight problems."

Related Links

To read more about how being overweight affects your health, visit MayoClinic.com.

http://www.starmonitor.com/index2.html

http://www.starmonitor.com