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Peer-reviewedCC BY-NC-ND 4.0International Journal of Obesity (2005)

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

  • Michelle D. Pang1
  • Jacco J. A. J. Bastings1
  • Johan W. E. Jocken1
  • Joanne A. Harrold2
  • Jason C. G. Halford2,3
  • Louise Kjølbæk4
  • Anne Raben4
  • Tanja C. M. Adam5
  • Ellen E. Blaak1
  • Gijs H. Goossens1
5 affiliations
  1. 1Department of Human Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
  2. 2Department of Psychology, Institute of Population Health, University of Liverpool, Liverpool, UK
  3. 3School of Psychology, University of Leeds, Leeds, UK
  4. 4Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
  5. 5Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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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 (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).

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Cite

BibTeXRIS
BibTeX
@article{pang2026longterm,
  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}},
  author = {Michelle D. Pang and Jacco J. A. J. Bastings and Johan W. E. Jocken and Joanne A. Harrold and Jason C. G. Halford and Louise Kjølbæk and Anne Raben and Tanja C. M. Adam and Ellen E. Blaak and Gijs H. Goossens},
  journal = {International Journal of Obesity (2005)},
  year = {2026},
  month = jun,
  doi = {10.1038/s41366-026-02117-z},
  url = {https://doi.org/10.1038/s41366-026-02117-z},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Long-term effect of sweeteners and sweetness enhancers on gene expression markers of adipose tissue function, adipocyte morphology, and metabolic health: a SWEET substudy
AU  - Michelle D. Pang
AU  - Jacco J. A. J. Bastings
AU  - Johan W. E. Jocken
AU  - Joanne A. Harrold
AU  - Jason C. G. Halford
AU  - Louise Kjølbæk
AU  - Anne Raben
AU  - Tanja C. M. Adam
AU  - Ellen E. Blaak
AU  - Gijs H. Goossens
PY  - 2026
DA  - 2026/06/02
JO  - International Journal of Obesity (2005)
DO  - 10.1038/s41366-026-02117-z
UR  - https://doi.org/10.1038/s41366-026-02117-z
AB  - 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).
SN  - 0307-0565
SN  - 1476-5497
ER  -