Lora Heisler is the Chair of Human Nutrition and Director of Research at the Rowett Institute, University of Aberdeen, Scotland, where she also leads the Obesity and Food Choice research theme. She is an internationally recognized scientist whose work has made seminal contributions to understanding the neurobiology of energy balance, appetite regulation and glucose homeostasis, with the aim of identifying novel targets for the treatment of obesity and type 2 diabetes.
Professor Heisler obtained her B.S. from Boston University, an MSc from the London School of Economics and Political Science, and her PhD from Tufts University in 1997. She completed postdoctoral fellowships at the University of California, San Francisco, and at Beth Israel Deaconess Medical Center, Harvard Medical School. In 2001, Heisler joined the faculty at Harvard Medical School, where she established her independent research laboratory. She subsequently relocated her group to the University of Cambridge, UK, in 2004, where she spent the next decade as a Wellcome Trust Senior Fellow, developing a strong and internationally recognized research programme in the neurobiology of energy balance. In 2013, her laboratory moved to the Rowett Institute to benefit from the Institute’s comprehensive strengths in obesity research, spanning molecular, physiological, and translational approaches.
Heisler’s research has yielded influential discoveries in brain circuits controlling body weight and glucose regulation. Notably, she has elucidated key mechanisms by which serotonin signaling in the brain can be harnessed for the treatment of obesity and diabetes, including defining how the anti-obesity drug d-fenfluramine exerts its effects and identifying novel serotonin receptor targets with therapeutic potential. Her work exemplifies the successful translation of fundamental neuroscience into clinically relevant strategies.
Lora Heisler’s contributions have been recognized with Outstanding Scientific Achievement Awards from the Obesity Society and the American Diabetes Association, and she was elected a Fellow of the Royal Society of Edinburgh in 2016. In addition, Professor Heisler has served on multiple journal editorial boards and was appointed Deputy Editor of Molecular Metabolism in 2018.
New Insights into the Drug Treatment of Obesity
Obesity represents a major global health and economic challenge, and glucagon-like peptide-1 receptor (GLP-1R) agonists such as semaglutide (Wegovy) have emerged as highly effective therapeutics through their actions to reduce food intake. Although GLP-1R agonists clearly induce weight loss, the mechanisms through which they alter feeding behaviour and body composition remain incompletely understood. Here, we investigated the impact of short- and longer-term semaglutide treatment, as well as drug withdrawal, on food choice, body composition, and underlying neurocircuit mechanisms in dietary-induced obese mice.
As expected, semaglutide administration significantly reduced body weight, driven predominantly by decreases in fat mass and, to a lesser extent, lean mass. Correspondingly, semaglutide lowered white and brown adipose tissue depots and reduced liver weight. Bone mineral density and bone mineral content were unchanged, while reductions in individual muscle weights did not translate into impaired muscle function. These findings indicate that semaglutide produces rapid weight loss associated with tissue-specific effects.
In studies assessing drug withdrawal, semaglutide cessation resulted in rapid rebound weight gain, with fat mass exceeding pre-treatment levels and lean mass showing limited recovery. Conversely, less frequent semaglutide dosing over two months maintained robust fat-mass reductions while preventing lean-mass loss, suggesting dose-pattern optimisation may mitigate adverse body-composition effects.
To identify neural substrates engaged by GLP-1R agonists, we examined brainstem circuits and found that a subset of dorsal vagal complex (DVC) GLP-1R-expressing neurons is GABAergic. Functional manipulation of GABA DVC → hypothalamic arcuate nucleus (ARC) projections revealed their potent bidirectional control of food intake. Moreover, chemogenetic inhibition of GABA DVC neurons partially attenuated liraglutide- and semaglutide-induced hypophagia, demonstrating that this circuit contributes to GLP-1R–mediated feeding suppression.
Together, these findings reveal integrated metabolic and neurocircuit mechanisms through which GLP-1R agonists regulate energy balance and highlight GABA DVC pathways as a contributor to the therapeutic benefit.
