Differential Effects of High Methionine Diet on Biochemical Parameters in Normal and Diabetic Rat Models

Abstract

This study investigated the organ-specific effects of a high-methionine (HM) diet in streptozotocin (STZ)-induced diabetic rats, focusing on hepatic and renal metabolic adaptations. Male Wistar rats were divided into four groups (n=8/group): normal control, HM (2% methionine), STZ-diabetic, and HM+STZ. Over 12 weeks, HM supplementation in diabetic rats significantly reduced hepatic triglyceride accumulation (42.00±7.71 vs. 20.76±3.63 mg/g tissue, P<0.01), coinciding with AMP-activated protein kinase (AMPK) activation (1.96-fold, P<0.05) and downregulation of lipogenic genes (sterol regulatory element-binding protein 1c ↓63.2%, P<0.05). Conversely, HM exacerbated diabetic nephropathy, elevating urinary albumin-creatinine ratio (411.90±88.86 vs. 238.41±62.52 mg/g, P<0.05) and glomerulosclerosis index (2.5±0.5 vs. 1.8±0.4, P<0.001). Hyperhomocysteinemia (105.69±33.81 μmol/L) persisted across HM groups without altering folate/vitamin B12 levels (P>0.05). These findings demonstrate a striking dichotomy: HM diet ameliorates hepatic steatosis through AMPK-mediated lipid modulation while accelerating renal injury via homocysteine-dependent pathways. The results highlight the need for organ-specific nutritional strategies in diabetes management.

Keywords

methionine metabolism - diabetic complications - hepatic steatosis - diabetic nephropathy - AMPK signaling

Publication History

Received: 18 April 2025

Accepted after revision: 13 August 2025

Article published online:
29 October 2025

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