LOS ANGELES — A brain counter-regulatory mechanism may be at play in weight loss plateaus with GLP-1 receptor agonists.
“Obesity and its comorbidities have been rising rapidly in the United States and other developed countries. At these rates, it is too fast to be due to genetic factors alone,” Olivia Farr, PhD, instructor in medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, said during a presentation at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. There are many external and internal factors “and a lot of the internal factors can be tied into the brain,” she said.
Farr said there are five major networks in the brain that have been associated with obesity and other metabolic disorders: homeostatic (hypothalamus); cognitive control (prefrontal cortex); emotion and memory (amygdala, hippocampus); reward (ventral tegmental area, striatum); and attention (visual and parietal cortices).
Farr’s group has studied the GLP-1 hormone, which is produced by the gut. GLP-1 “acts in any number of organs and, importantly, I would argue in the brain,” she said.
Farr and colleagues confirmed that GLP-1 receptors are found in the human brain and then went on to determine if it is functional. And, the researchers did confirm that GLP-1 alters the brain when shown highly desirable food cues by functional MRI task and when showing study participants randomly displayed images of highly desirable foods, low desirable foods and non-foods.
A brain counter-regulatory mechanism may be at play in weight loss plateaus with GLP-1 receptor agonists.
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Farr’s subsequent research evaluated the 3 mg dose of liraglutide (Saxenda, Novo Nordisk) in patients with and without diabetes.
“What we saw in the first analysis was that there was no change in brain activation, but at 5 weeks patients are losing weight significantly, and once we controlled for weight we actually see an increase in reward-related orbital frontal cortex activation to highly palatable food,” Farr said.
This finding leads Farr to believe that this is a counter-regulatory measure “that later leads to the plateau in weight loss as seen with liraglutide a little later in time,” she said. “This could be an early identifier of the change that leads to patients not continuously losing weight.”
Further research is needed to define how changes happen with time that would lead to an understanding of weight loss plateauing, she said.
“We believe that the brain is a driver behind the epidemic of obesity,” Farr said, noting that the brain and how it interacts with molecules and pharmaceuticals must be studied.
Farr is the first awardee of the Young Investigator Award jointly given by the Journal of Metabolism and the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. To be considered, an individual must submit a paper to the journal Metabolism, ask to be considered and have one’s mentor submit a letter. The awarded is chosen by blind voting, according to Christos S. Mantzoros, MD, DSc, PhD, Editor in Chief of Metabolism.
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Farr OM. Brain and Metabolism: The Next Frontier. Presented at: World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease; December 4-7, 2019; Los Angeles.
Farr OM, et al. Diabetes Obes Metab. 2019;doi:10.1111/dom.13827.
Disclosure: Some of Farr’s studies were funded by Novo Nordisk.