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

Autor(es): Pang MD, Bastings JJAJ, Jocken JWE, Harrold JA, Halford JCG, Kjolbak L, Raben A, Adam TCM, Blaak EE, Goossens GH; SWEET consortium.
Nombre de publicación : Int J Obes (Lond). 2026 Jun 2.https://doi.org/10.1038/s41366-026-02117-z
Año de publicación : 2026

Abstract:

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 (CEBPɑP = 0.004), fatty acid uptake (LPL and SREBF1, both P < 0.001), fatty acid synthesis (FASN and SCD, both P < 0.001), intracellular lipolysis (ATGLP < 0.001; HSLP = 0.001), leptin (LEPP < 0.001), and mitochondrial function (CSP = 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.

 

Summary:

This SWEET substudy investigated whether replacing sugar with low- and no-calorie sweeteners (LNCS) and sweetness enhancers during a 10-month weight-maintenance period following a 2-month weight loss phase affects adipose tissue function and metabolic health in adults with overweight or obesity. The study included 83 participants, of whom 52 completed the full intervention.

Following the initial weight-loss phase, which resulted in improvements across several metabolic health markers, participants consuming LNCS-containing foods and beverages during the weight-maintenance phase tended to regain less weight than those who avoided LNCS.

LNCS consumption was associated with a smaller increase in adipose tissue expression of the lipid uptake gene LPL and a decrease in expression of the lipolysis-related gene ABHD5, suggesting modest alterations in adipose tissue lipid turnover. Nevertheless, no differences were observed between the groups in adipocyte size, markers of inflammation or oxidative metabolism, sweet taste receptor expression, or whole-body, hepatic, and skeletal muscle insulin sensitivity.

Overall, the findings suggest that the long-term use of LNCS as a replacement for sugar during weight maintenance does not adversely affect adipose tissue morphology or metabolic health and may support improved weight maintenance following weight loss.

 

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