Do Sweeteners Help Limit Weight Regain After a Diet?

Weight loss reduces the size of fat cells and improves sensitivity to insulin, a key hormone for regulating blood sugar. These changes are accompanied by a decrease in the activity of several genes in adipose tissue, involved in fat formation, storage, and breakdown. Among these genes, some control the production of leptin, a hormone that regulates hunger, or the functioning of mitochondria, the cells’ energy powerhouses.

A recent study examined whether replacing sugar with sweeteners or sweet taste enhancers could influence these mechanisms during a weight maintenance phase after a weight loss diet. For ten months, overweight or obese adults followed a healthy diet limited in added sugars, with or without sweeteners. The results show that the group using sweeteners tends to regain less weight than the one consuming sugar, with an average difference of nearly three kilograms. This observation is partly explained by changes in the expression of certain genes in adipose tissue.

Indeed, in participants consuming sweeteners, the increase in the activity of the LPL gene, which promotes fat storage, is less pronounced. Additionally, the activity of the ABHD5 gene, which participates in the breakdown of fats inside cells, decreases. These two genes play a key role in lipid metabolism: the first allows fat cells to capture circulating fatty acids in the blood, while the second activates enzymes that release these stored fatty acids. A decrease in their activity could therefore limit fat storage and release, contributing to better weight control.

Furthermore, the lesser increase in LPL gene activity is associated with a more moderate rise in fasting glycemia, i.e., the blood sugar level after an overnight fast. This suggests that sweeteners could help stabilize this important metabolic parameter. However, no differences were observed between the two groups regarding the size of fat cells, insulin sensitivity, or adipose tissue inflammation.

These results indicate that, in the long term, sweeteners could modify certain molecular mechanisms related to fat metabolism without affecting the structure of fat cells or the body’s response to insulin. They thus open avenues for better understanding how these sugar substitutes act on metabolic health, particularly in people seeking to stabilize their weight after a diet.

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DOI: https://doi.org/10.1038/s41366-026-02117-z

Title: Long-term effect of sweeteners and sweetness enhancers on gene expression markers of adipose tissue function, adipocyte morphology, and metabolic health: a SWEET substudy

Journal: International Journal of Obesity

Publisher: Springer Science and Business Media LLC

Authors: Michelle D. Pang; Jacco J. A. J. Bastings; Johan W. E. Jocken; Joanne A. Harrold; Jason C. G. Halford; Louise Kjølbæk; Anne Raben; Tanja C. M. Adam; Ellen E. Blaak; Gijs H. Goossens;