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Peer-reviewedCC BYJournal of diabetes and metabolic disorders

Continuous caloric restriction and diet replacement but not alternate-day fasting may enhance susceptibility to glucose intolerance, dyslipidemia and cell stress under renewed high-fat diet.

5 affiliations
  1. 1Graduate Program in Integral Health Care (PPGAIS/UNICRUZ/URI-Erechim/UNIJUÍ), Regional University of Northwestern Rio Grande do Sul State (UNIJUÍ), Ijuí, RS Brazil.
  2. 2Brigham and Women's Hospital, Boston, MA USA.
  3. 3Universidade Regional do Noroeste do Estado do Rio Grande do Sul (UNIJUI), Bairro Universitário, Rua do Comercio, 3000 - Bairro Universitário, Ijui, 98700-000 Rio Grande do Sul Brazil.
  4. 4Graduate Program in Mathematical and Computational Modeling (PPGMMC), Regional University of Northwestern Rio Grande do Sul State (UNIJUÍ), Ijuí, RS Brazil.
  5. 5National Institute of Science and Technology - INCT Physical (In)activity and Health, CNPq, Brazil.

Abstract

Background

Weight regain affects most individuals attempting to treat obesity and its comorbidities, and it is associated with increased risk of metabolic and cardiovascular diseases. Several strategies have been proposed to induce weight loss, including caloric restriction (CCR), diet replacement (DR) and alternate-day fasting (ADF).Aim

To compare these approaches in terms of weight maintenance and metabolic, oxidative, and inflammatory outcomes.Methods

Male Wistar rats underwent a three-phase protocol. First, animals received a high-fat diet (HFD) for eight weeks to induce obesity. Second, they were divided into four groups: ad lib-HFD (continued HFD), R-HFD (30% reduction of HFD w/w), ADF-HFD (24 h fasting alternating with 24 h ad libitum HFD), and ad lib-LFD (DR via ad libitum access to low-fat chow) for six weeks. Finally, all groups returned to free access to HFD for four weeks.Results

All interventions delayed weight gain; however, discontinuation led to rapid weight regain. Under renewed HFD ad libitum exposure, CCR and DR induced higher susceptibility to dyslipidemia, as shown by the temporal analysis. These strategies also impaired hepatic and adipose antioxidant and anti-inflammatory responses and heightened lymph node stress upon return to unlimited offer of obesogenic diet. In contrast, ADF appeared to confer partial protection against the metabolic complications of weight rebound.Conclusions

Despite similar weight-loss efficacy, ADF may better preserve metabolic homeostasis during weight regain.Supplementary information

The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02112-1.

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BibTeX
@article{beuren2026continuous,
  title = {{Continuous caloric restriction and diet replacement but not alternate-day fasting may enhance susceptibility to glucose intolerance, dyslipidemia and cell stress under renewed high-fat diet.}},
  author = {Andrea Cristiani Beuren and Jaíne Borges Dos Santos and Natascha Fill Izolan and Lílian Corrêa Costa-Beber and Lucas Machado Sulzbacher and Matias Nunes Frizzo and Pauline Brendler Goettems-Fiorin and Thiago Gomes Heck and Mirna Stela Ludwig},
  journal = {Journal of diabetes and metabolic disorders},
  year = {2026},
  month = oct,
  doi = {10.1007/s40200-026-02112-1},
  url = {https://europepmc.org/article/MED/42923472},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Continuous caloric restriction and diet replacement but not alternate-day fasting may enhance susceptibility to glucose intolerance, dyslipidemia and cell stress under renewed high-fat diet.
AU  - Andrea Cristiani Beuren
AU  - Jaíne Borges Dos Santos
AU  - Natascha Fill Izolan
AU  - Lílian Corrêa Costa-Beber
AU  - Lucas Machado Sulzbacher
AU  - Matias Nunes Frizzo
AU  - Pauline Brendler Goettems-Fiorin
AU  - Thiago Gomes Heck
AU  - Mirna Stela Ludwig
PY  - 2026
DA  - 2026/10/21
JO  - Journal of diabetes and metabolic disorders
DO  - 10.1007/s40200-026-02112-1
UR  - https://europepmc.org/article/MED/42923472
AB  - Background  Weight regain affects most individuals attempting to treat obesity and its comorbidities, and it is associated with increased risk of metabolic and cardiovascular diseases. Several strategies have been proposed to induce weight loss, including caloric restriction (CCR), diet replacement (DR) and alternate-day fasting (ADF).Aim  To compare these approaches in terms of weight maintenance and metabolic, oxidative, and inflammatory outcomes.Methods  Male Wistar rats underwent a three-phase protocol. First, animals received a high-fat diet (HFD) for eight weeks to induce obesity. Second, they were divided into four groups: ad lib-HFD (continued HFD), R-HFD (30% reduction of HFD w/w), ADF-HFD (24 h fasting alternating with 24 h ad libitum HFD), and ad lib-LFD (DR via ad libitum access to low-fat chow) for six weeks. Finally, all groups returned to free access to HFD for four weeks.Results  All interventions delayed weight gain; however, discontinuation led to rapid weight regain. Under renewed HFD ad libitum exposure, CCR and DR induced higher susceptibility to dyslipidemia, as shown by the temporal analysis. These strategies also impaired hepatic and adipose antioxidant and anti-inflammatory responses and heightened lymph node stress upon return to unlimited offer of obesogenic diet. In contrast, ADF appeared to confer partial protection against the metabolic complications of weight rebound.Conclusions  Despite similar weight-loss efficacy, ADF may better preserve metabolic homeostasis during weight regain.Supplementary information  The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02112-1.
SN  - 2251-6581
ER  -