8:16 Time Restricted Feeding and 5:2 Intermittent Fasting Exert Beneficial Metabolic Effects on Lipid Profile and Endoplasmic Reticulum Stress in High Fructose-Consuming Rats

Abstract

We aimed to investigate and compare the effects of two different frequently utilized intermittent fasting (IF) protocols (8:16 and 5:2) applied for eight weeks on weight loss, metabolic indices, serum/liver sterol regulatory protein (SREBP) levels, and endoplasmic reticulum stress (ERS) markers in normal and high-fructose (HF) fed rats. Sixty male, Wistar rats were divided into six groups (n = 60): Control(C), 8:16 (8 h ad libitum and 16 h fasting), 5:2 (2 days food restriction followed by 5 days ad libitum-feeding), HF (high-fructose, 20% drinking water, eight weeks), 8:16 + HF, 5:2 + HF groups. IF protocols were applied for eight weeks. Serum and liver SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride (TG), and serum protein kinase RNA-like endoplasmic reticulum kinase (PERK), protein glucose-regulated protein 78 (GRP78), and X-box binding protein 1 (XBP1) levels were determined by commercial kits. The body weight (BW) and visceral fat lowering effects of 5:2 diet was more prominent compared to 8:16 TRF. Both IF protocols decreased serum SREBP-2, ACC, TG, cholesterol levels (p < 0.05). HF induced weight gain and increment in serum glucose which was reversed by 8:16 IF. The weight loss effect of 5:2 IF was also more prominent in HF. Serum and liver SREBP-1c, SREBP-2, cholesterol, TG levels were higher in HF group than C (p < 0.05). Both IF regimens decreased serum and liver SREBP-1, SREBP-2, ACC, TG, cholestreol levels in rats subjected to HF diet (p < 0.05). Although IF regimens did not cause ERS; they reversed elevated ERS induced by HF diet. Both IF protocols have beneficial effects on both normal and HF consuming rats, being superior to each other on several parameters. © The Author(s) 2025.