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Background <p>This study aimed to investigate the effects of alternate-day fasting (ADF) on body weight (BW), fat distribution, and key molecular markers related to endoplasmic reticulum stress&#xa0;(ERS) and sterol regulatory element-binding protein-1(SREBP-1) in young&#xa0;(3-month-old) and middle-aged&#xa0;(16-month-old) rats.</p> Methods <p>Thirty-two male Wistar rats were divided into four groups: Group1 (ad libitum(AL)-fed young rats), Group2 (ADF-young rats), Group3 (AL-fed middle-aged rats), and Group4&#xa0;(ADF-middle-aged rats). ADF was implemented as a 24&#xa0;h feeding period followed by 24&#xa0;h of fasting for 28&#xa0;days. Serum and liver samples were analyzed via ELISA for SREBP-1, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6&#xa0;(ATF6), and glucose-regulated protein 78&#xa0;(GRP78) levels.</p> Results <p>Compared with Group-1, Group-3 had significantly greater BW and retroperitoneal fat content (<i>p</i> = 0.001). ADF reduced BW in young rats (Group-2 vs. Group-1,<i>p</i> = 0.015) but not in middle-aged rats (Group-4 vs. Group-3,<i>p</i> = 0.073). ADF significantly reduced fat accumulation in middle-aged rats (Group-4 vs<i>.</i> Group-3 <i>p</i> = 0.001), although fat accumulation was greater in middle-aged rats than in young rats (<i>p</i> = 0.001). Serum and liver PERK,GRP78,ATF6, and SREBP-1 levels were significantly greater in AL-fed middle-aged rats (Group-3 vs<i>.</i> Group-1,<i>p</i> &lt; 0.05), indicating that ERS and lipid dysregulation increase with age. ADF significantly reduced these markers in middle-aged rats (Group-4 vs<i>.</i> Group-3,<i>p</i> &lt; 0.05), suggesting a protective effect. Additionally, ADF lowered serum and liver SREBP-1 levels in young rats (Group-2 vs<i>.</i> Group-1,<i>p</i> = 0.003), highlighting its role in lipid metabolism regulation.</p> Conclusions <p>ADF appears to be a promising nonpharmacological approach for mitigating age-related metabolic and molecular disturbances. Further research is warranted to explore its long-term effects and translational potential in human aging.</p> Graphical Abstract <p></p>

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Alternate-Day Fasting Modulates Endoplasmic Reticulum Stress and Lipid Metabolism in Young and Middle-Aged Rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月15日

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  • Ozgen Kilic-Erkek,
  • Gulsah Gundogdu,
  • Tunahan Anber,
  • Hasan Akca,
  • Yavuz Dodurga,
  • A. M. Abd El-Aty

摘要

Background

This study aimed to investigate the effects of alternate-day fasting (ADF) on body weight (BW), fat distribution, and key molecular markers related to endoplasmic reticulum stress (ERS) and sterol regulatory element-binding protein-1(SREBP-1) in young (3-month-old) and middle-aged (16-month-old) rats.

Methods

Thirty-two male Wistar rats were divided into four groups: Group1 (ad libitum(AL)-fed young rats), Group2 (ADF-young rats), Group3 (AL-fed middle-aged rats), and Group4 (ADF-middle-aged rats). ADF was implemented as a 24 h feeding period followed by 24 h of fasting for 28 days. Serum and liver samples were analyzed via ELISA for SREBP-1, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF6), and glucose-regulated protein 78 (GRP78) levels.

Results

Compared with Group-1, Group-3 had significantly greater BW and retroperitoneal fat content (p = 0.001). ADF reduced BW in young rats (Group-2 vs. Group-1,p = 0.015) but not in middle-aged rats (Group-4 vs. Group-3,p = 0.073). ADF significantly reduced fat accumulation in middle-aged rats (Group-4 vs. Group-3 p = 0.001), although fat accumulation was greater in middle-aged rats than in young rats (p = 0.001). Serum and liver PERK,GRP78,ATF6, and SREBP-1 levels were significantly greater in AL-fed middle-aged rats (Group-3 vs. Group-1,p < 0.05), indicating that ERS and lipid dysregulation increase with age. ADF significantly reduced these markers in middle-aged rats (Group-4 vs. Group-3,p < 0.05), suggesting a protective effect. Additionally, ADF lowered serum and liver SREBP-1 levels in young rats (Group-2 vs. Group-1,p = 0.003), highlighting its role in lipid metabolism regulation.

Conclusions

ADF appears to be a promising nonpharmacological approach for mitigating age-related metabolic and molecular disturbances. Further research is warranted to explore its long-term effects and translational potential in human aging.

Graphical Abstract