Abstract: Purpose: To evaluate the protective effect of dietary methionine restriction (MR) on the pancreas of obese mice induced by high-fat diet. Methods: Totally 210 male C57BL/6J mice were divided into a control group (CON: 0.86% methionine + 4% fat; n = 30) and a high-fat diet group (HF: 0.86% methionine + 20% fat; n = 180). Obesity was successfully induced in 120 of the HF diet fed mice, and the obese mice were further randomly divided into an HF group, an HF + MR group (0.17% methionine + 20% fat), a control diet group (C*: 0.86% methionine + 4% fat) and a C* + MR group ( 0.17% methionine + 4% fat). A subset of animals in each of the four groups were euthanized at 8, 16 and 24 weeks. Glucose tolerance was determined at 24 weeks. Fasting blood glucose and plasma insulin levels, hydrogen sulfide (H2S) levels and redox indicators in plasma and pancreas were investigated. Quantitative real-time polymerase chain reaction (PCR) was used to determine the expression of genes related to insulin secretion and endoplasmic reticulum stress. Results: MR significantly reduced body mass and increased feed and energy intakes in mice (P < 0.05); decreased fasting blood glucose and plasma insulin levels, glucose tolerance and insulin resistance index (P < 0.05); increased H2S levels in plasma and pancreas and improved redox status (P < 0.05); up-regulated the mRNA expression of cystathionine-caseo-lyase (CSE), cystathie-base-synthase (CBS), v-maf musculoaponeurotic fibrosarcoma oncogene homologue (MafA), pancreatic duodenal homeobox-1 (Pdx-1) and B-cell lymphoma 2 (Bcl-2), and down-regulated the mRNA expression of Bcl-2 associated protein X (Bax), X-box binding protein-1 (Xbp-1), C/EBP homologous protein (CHOP), and inositol requiring enzyme 1α (IRE1α) (P < 0.05). Interestingly, the HF + MR and C* + MR groups showed similar trends in all the above indicators. Conclusion: MR can protect the pancreas and promote insulin secretion by improving endoplasmic reticulum stress and redox status in pancreatic tissue of obese mice.

Key words: methionine restriction, pancreas, obesity, insulin resistance, endoplasmic reticulum stress