Trans fatty acids alter renal health in TGFβ3 mice with fibrosis revealed by metabolomics and lipidomics.

Trans-fatty acids, abundant in Western diets, are detrimental to kidney health, yet their impact on renal metabolic and lipid homeostasis remains poorly understood. Here, we examine the effects of a trans-fat diet on renal function using wild-type, and mice heterozygous for transforming growth factor β3 (Tgfβ3) deletion that present kidney damage and fibrosis. Using integrated metabolomic, lipidomic, molecular, and cellular analyses, we show that in wild-type mice, the trans-fat diet disrupted renal lipid metabolism, characterized by a marked depletion of serum triglycerides, alterations in lipid-synthesis genes in the kidney, and metabolic signatures of mitochondrial dysfunction. In Tgfβ3-heterozygous kidneys, the trans-fat diet exacerbated oxidative stress and was associated with severe depletion of lipid species and aggravated podocyte loss. Notably, the combination of trans-fat consumption and Tgfβ3 deficiency caused intracellular accumulation of enlarged lipid droplets and taurine depletion in the kidneys. Together, a trans-fat-rich diet markedly intensifies the renal injury associated with Tgfβ3 deficiency.