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

Background/Objectives We investigated the effects of sweeteners and sweetness enhancers (S&SEs) in replacement of sugar on gene expression markers of adipose tissue (AT) function, adipocyte morphology, and metabolic health in adults during weight maintenance (WM) following weight loss (WL).

Subjects/Methods As part of a randomized controlled trial (European SWEET-project), 83 adults were enrolled in the study, which consists of a dietary intervention, comprising a 2-month WL-phase and a 10-month WM-phase during which participants followed a healthy diet (<10E%-added sugar) with (S&SEs group) or without S&SEs (sugar group). At baseline, after WL, and at the end of WM, we determined body composition, whole-body/tissue-specific insulin sensitivity (oral glucose tolerance test), abdominal subcutaneous adipocyte size and AT gene expression.

Results WL decreased adipocyte size and improved insulin sensitivity (both P < 0.001), which was accompanied by a significant downregulation of genes involved in adipogenesis (CEBPɑ, P = 0.004), fatty acid uptake (LPL and SREBF1, both P < 0.001), fatty acid synthesis (FASN and SCD, both P < 0.001), intracellular lipolysis (ATGL, P < 0.001; HSL, P = 0.001), leptin (LEP, P < 0.001), and mitochondrial function (CS, P = 0.048) in AT. The S&SEs-group tended to regain less weight than the sugar group during the WM-phase (3.0 ± 1.2 vs. 5.9 ± 1.0 kg, respectively; P = 0.050). During the WM-phase, the S&SEs group showed a less pronounced increase in AT LPL gene expression (P = 0.041), while ABHD5 expression decreased compared to the sugar group (P = 0.036). No group differences in adipocyte size, expression of genes involved adipogenesis/oxidative metabolism/inflammation, the sweet taste receptor TAS1R3 and insulin sensitivity were found.

Conclusions S&SE-intake during a 10-month WM-phase following WL altered AT gene expression of lipolytic markers, without affecting adipocyte morphology and insulin sensitivity in adults with overweight/obesity.

Trial registration ClinicalTrials.gov NCT04226911, Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety (SWEET).