Work

Dietary methylglyoxal induces renal lipotoxicity primarily through adipose tissue dysfunction in mice fed normal or obesogenic high-fat diets

Year: 2025

Type: article

Abstract: • HFD alone caused non-lipotoxic kidney injury without inducing significant adipose tissue dysfunction. • Dietary methylglyoxal (MG) induced renal lipotoxicity and injury in mice, independent of the normal or obesogenic high-fat diet status. • MG-induced kidney damage is primarily mediated by promoting adipose tissue dysfunction, characterized by impaired angiogenesis and increased fibrosis. Unhealthy dietary patterns may impair renal function through elevated dietary methylglyoxal (MG) and advanced glycation end products (AGEs). While adipose tissue stores triglycerides (TG), its dysfunction promotes ectopic lipotoxicity, a process exacerbated by MG or AGEs. This study investigated if long-term dietary MG causes renal damage, mediated by adipose tissue dysfunction and ectopic lipid deposition. Eight-week-old male ICR mice were randomized into four groups for 52 weeks: normal diet and obesogenic high-fat diet (HFD), each with or without 1% MG in drinking water. HFD significantly increased MG-AGEs in both adipose tissue and kidneys. Although it caused adipocyte hypertrophy, the HFD-induced renal injury was observed despite the lack of kidney lipid accumulation. Concurrently, MG administration induced renal lipotoxicity and injury, manifested by increased TG concentrations in both the cortex and medulla. In HFD-fed mice, MG further exacerbated adipose tissue dysfunction by inhibiting angiogenesis and increasing interstitial collagen accumulation. Moreover, the MG co-administration reduced adipocyte size, a finding contrary to the hypertrophy caused by HFD alone. Furthermore, in the kidneys of these HFD-fed mice, MG led to increased medullary TG concentration and elevated collagen expression. In conclusion, HFD alone caused non-lipotoxic kidney injury without significant adipose dysfunction. However, MG administration consistently induced adipose tissue dysfunction and progressive renal lipotoxicity regardless of the diet. These findings suggest that MG-induced renal damage is primarily mediated by the dysfunction of adipose tissue, establishing a critical link between dietary MG intake and kidney disease progression, independent of obesogenic diet status.

Source: The Journal of Nutritional Biochemistry

DOI: 10.1016/j.jnutbio.2025.110244

Authors: Medhavi Paramita Kondanna, Yu-Ho Chang, Hsin-Yi Yang, Chi-Hao Wu, Wan-Ju Yeh

Institutions: National Taiwan Normal University, Ministry of Health and Welfare, Taipei Hospital, Fu Jen Catholic University

Language: English

Topic: Advanced Glycation End Products research

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,980