Richard Bergman, PhD, discusses the interplay of free fatty acids, adipose tissue, and insulin resistance in understanding diabetes.
In his key note presenstation, Oct. 22, at the Cardiometabolic Health Congress, titled, “Key Elements of Glucose Metabolism,” Richard Bergman, PhD, discussed the role of free fatty acids, beta cells, and the process of insulin sensitivity in the development of diabetes and new insight based on research, partly conducted by his own team.
Bergman, Keck Professor of Medicine, Keck School of Medicine, University of Southern California.
Bergman’s lab has performed work on animal models, specifically dogs, to study the effects of high fat diets on insulin function. Dog models offer a few advantages in this research, he said: there is a 90% similarity in genetic material between humans and dogs, and using dog models allows for longitudinal study, and access to the portal vein, he said.
For the research, his team fed the dogs a high fat diet and increased their caloric intake, which resulted in a 10-15% body weight increase. The study also administered rimonabant to the dogs fed the fatty diet to examine the effects. The researchers analyzed and monitored two types of fat — visceral fat and subcutaneous fat. They found that both increased in different manners.
The dogs’ subcutaneous fat had nu merous cells that werelarger in size than others, likewise, the visceral fat had large sized cells develop but had an even higher amount of large cells. However, when the dogs were given rimonabant, the cells in both fat tissues developed normally. Giving the rominabant also helped to reduce inflammation. The large cells in the visceral fat played a role in creating insulin resistance, he said.
After six weeks of feeding the dogs the high fat diet, the researchers found that fasting glucose levels were normal, but insulin sensitivity was reduced, which would then cause a pancreatic reaction. What predicted a rise in insulin resistance was the rate at which insulin was cleared by the liver, he said.
The high fat diet effected the pancreases ability to clear insulin from the liver, which then results in the liver having too much fat present and procuces insulin conditions.
The elevated level of insulin in the blood may further cause insulin resistance, which is then compensated by an increase in free fatty acids (FFA). Specifically, an increase in nocturnal free fatty acids may be particularly destructive. These FFAs may exacerbate insulin resistance, which then cause beta cells to create more insulin, resulting in hyperinsulinemia.
Bergman’s team had the hypothesis that nocturnal FFAs cause insulin resistance, which then may result in increased cardiovascular risk. At night, particularly 3 a.m., the brain delivers fatty acids to the liver from the visceral depot, he explained. To study this in further detail, his lab performed omentectomies, which determine that visceral fat cells were critical in determining insulin sensitivity.
The team also followed how insulin is delivered to the muscles and problems that can occur with increased fat levels. The process of delivering insulin to the muscles requires beta cells to secret insulin across the endothelial barrier, which causes an increase in interstitial insulin to stimulate glucose uptake. In a study, the team hypothesized that a delay in insulin action may occur in the capillary barrier and result in insulin not properly being delivered to the muscle. The study had researchers inject insulin directly into the muscle. Results demonstrated that by doing so insulin uptake functioned properly at the muscle.
A study focusing on how obesity affected insulin delivery to muscles, uncovered that fat interferes with insulin’s ability to cross into the interstitial fluid.
The findings are consistent with other research presented at the conference, which demonstrates that the rise in boy fat due to high fat diets is a key component in the development of diabetes and insulin-focused metabolic conditions.
A last feature of the presentation, was a discussion of the Body Mass Index tool as an accurate measure of body fat. Bergman mentioned that the BMI has a number of problems, including the fact that a standard reading may not represent different race groups well. Bergman and his team, instead came up with a different measuring system: The Body Adiposity Index.
This system focuses on two key indicators: hip circumference and height.