GLP-1 agonist drugs, such as Ozempic, have revolutionized the treatment of obesity and its associated comorbidities, including type 2 diabetes and fatty liver disease. These drugs mimic proteins naturally produced after eating and they act on the brain to stimulate feelings of satiety. However, the long-term effects and efficacy of these medications remain unclear. For instance, does drug resistance eventually develop? In other words, do these drugs lose their effectiveness after months or years of use? If so, does the weight loss reverse itself? The same question would apply to patients who voluntarily stop taking these medications.
Those who have lost weight through other methods are familiar with the challenge of regaining it. But why does this happen? Why doesn’t the body favor the new, lower weight condition rather than reverting to the previous higher weight condition? Researchers from ETH Zurich in Switzerland explored this phenomenon and discovered that adipocytes (fat cells) retain their pre-weight-loss pattern of gene expression. In other words, even after weight loss, fat cells continue to produce a pattern of RNAs and proteins that are consistent with their previous, higher-weight state rather than adapting to a pattern that discourages weight regain. This phenomenon, termed obesogenic memory, could be a key factor in rebound weight gain.
Reversing this “memory” with a drug that alters adipocyte gene expression could potentially reset the cells to favor a sustained low-weight state, leading to lasting weight loss.
