By Caroline Cencer
The laboratory of Professor of Molecular Physiology and Biophysics Alyssa Hasty recently published a study stressing the importance of glucose homeostasis in maintaining healthy body function. While examining blood glucose levels in diet-induced obese mice, co-first authors Nathan Winn and Matthew Cottam, a postdoctoral fellow and a recent graduate, respectively, discovered that weight cycling, the process of losing and regaining weight, impairs insulin secretion and decreases the body’s ability to control blood glucose levels.
We sat down with Winn to find out more about this research.
What issue/problem does your research address?
Repeated body weight fluctuations (i.e., weight cycling) are linked to a higher risk of a cluster of metabolic diseases than obesity alone. Prior work established that weight cycling worsens glucose intolerance, but the mechanisms are unclear. Thus, we aimed to systematically pinpoint the major control points and mechanisms by which weight cycling impairs glucose regulation.
What was unique about your approach to the research?
We determined glucose regulation using rigorous in vivo and ex vivo tests, which allowed for in-depth characterization of the mice. This was made possible through state-of-the-art core facilities and shared resources at Vanderbilt, including the VUMC Islet and Pancreas Analysis Core and the Vanderbilt Animal Metabolic Physiology Core.
What were your findings?
The pancreas releases hormones, including insulin, as a mechanism to control blood glucose levels. We found that, in weight cycling mice, pancreatic β-cells, which produce and secrete insulin, lose their key transcription factors and therefore their secretion function. This phenomenon is not observed in the β-cells of obese mice that had not weight cycled.
Our results suggest that repeated bouts of weight loss and weight regain in mice impair the pancreas’s ability to compensate for the increased body weight and to match insulin requirements to the level of glucose exposure. These findings may have clinical implications given that most obese individuals regain lost weight within a few years.
Where is this research taking you next? What will you personally be doing, or how will other researchers build on this work?
This work will spark future studies aimed at uncovering the mechanisms that control pancreatic adaptability to body weight fluctuations.
Funding
This work was funded by a Veterans Affairs Merit Award and American Heart Association Innovation Award.
Go further
This paper, “Weight Cycling Impairs Pancreatic Insulin Secretion but Does Not Perturb Whole-Body Insulin Action in Diet-Induced Obese Mice” was published in Diabetes in July 2022.