Mogroside-Rich Monk Fruit Extract Improves Glycemic Control Without Promoting Additional Weight Gain Compared With Sucralose and Sucrose in High-Fat Diet-Induced Obese Mice.

A high-fat diet (HFD) with excessive sugar intake contributes to obesity and type 2 diabetes, leading to increased use of non-nutritive sweeteners (NNS). However, evidence on their metabolic effects remains inconsistent, especially between natural and synthetic NNS. This study compared the effects of a natural NNS, monk fruit extract (MFE), with sucrose and synthetic sucralose, at equivalent sweetness on body weight and glucose homeostasis in HFD-induced obese mice. Male C57BL/6 mice were fed an HFD for 8 weeks to induce obesity, then randomized to receive distilled water (control), sucrose (266 g/L), MFE (1.1 g/L; ~50% mogroside V), or sucralose (0.36 g/L) in drinking water for another 8 weeks. Body weight, food and water intake, and oral glucose tolerance tests (OGTT) were assessed. At sacrifice, serum biochemistry, organs, tissues, and duodenal expression of sweet taste receptors (T1R2/T1R3) and glucose transporters (SGLT-1/GLUT2) were analyzed. The results showed that sucralose and sucrose further increased body weight gain, whereas MFE did not promote additional weight gain despite increased food intake. MFE significantly reduced fasting blood glucose, while sucralose impaired glucose tolerance, reflected by increased OGTT area under the curve. No significant differences in visceral adipose tissue weights or duodenal T1R2, T1R3, SGLT-1, and GLUT2 expression were observed among groups. In conclusion, MFE, within ADI-equivalent doses, improved fasting glycemia without promoting further weight gain compared with the HFD-control, whereas sucralose exacerbated obesity-related impaired glucose tolerance. These findings suggest that natural sweeteners such as MFE may represent a safer alternative to added sugars and synthetic NNS for weight management and glycemic control for obese subjects.