A recent study by researchers at UNC’s Gillings School of Global Public Health provides insight into the biochemical processes through which increased sugar intake may play an integral role in the promotion of obesity-related insulin resistance.
In a cell culture study with supportive data from rodents which were made obese by a high-fat diet, Makowski and colleagues demonstrated that elevated glucose metabolism through increased glucose transporter, called GLUT1, drives the inflammation of macrophages, the large white blood cells in tissue that ingest and engulf foreign particles, dying cells and infectious microorganisms.
The sugar glucose is known to be a critical component in the inflammatory response of macrophages in the human body. Little is known, however, about the contribution of glucose transporters (GLUTs) and the mechanisms that regulate glucose metabolism in the inflammatory response. The researchers found that GLUT1, which facilitates the transport of glucose across cell membranes, was present in macrophages at high levels in adipose and liver tissue samples from obese rodents, and they hypothesized that the reprogramming of metabolism could change the macrophages’ inflammatory response levels.
To increase glucose uptake into cells, the team over-expressed the GLUT1 transporter in a mouse macrophage cell line. Doing so resulted in elevated glucose uptake and metabolism through specific processes by the cells. Researchers also found that the resulting inflammation, which could be reversed by inhibiting glucose uptake or blocking oxidative stress, likely plays an important role in insulin resistance.
“This is an important finding because of the field’s increased interest in ‘metabolic reprogramming’ of immune cells,” Makowski said. “Understanding how macrophage substrate metabolism impacts inflammation is crucial to our being able to develop novel therapies for obesity and diabetes, and even cancer.”
UNC co-authors include, from the Gillings School’s Department of Nutrition, research associate Alex J. Freemerman, PhD, Amy R. Johnson, PhD, Gina N. Sacks, and J. Justin Milner; Erin L. Kirk, and Melissa Troester, PhD, from the Gillings School’s Department of Epidemiology. Troester is a member of the UNC Lineberger Comprehensive Cancer Center. Makowski also holds an appointment in the UNC School of Medicine. Other authors from Duke University’s Sarah Stedman Center for Nutrition and Metabolism are Andrew N. Macintyre, PhD, Pankuri Goraksha-Hicks, PhD, and Jeffery C. Rathmell, PhD.