In diabetic kidney disease, fat accumulates in the kidneys, leading to lipotoxicity and kidney damage. A recently published study by Ulf Eriksson's research group at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet shows that elevated levels of the protein VEGF-B in the kidney and adipose tissue correlate with increased fat accumulation in the kidney and impaired kidney function in patients with diabetic kidney disease.
"Antihypertensive drugs and diabetes medications can slow the progression of diabetic kidney disease, but they do not cure the disease. Our study suggests that activation of VEGF-B signaling in white adipose tissue and the kidney together contributes to higher release of fatty acids into the blood, leading to increased lipid accumulation in the kidney, a hallmark of diabetic kidney disease, which leads to impaired kidney function. Our data have clinical value as we propose that measuring VEGF-B levels and lipid accumulation in the kidney can help diagnose and identify patients at an early stage of diabetic kidney disease," says the study's first author Erika Folestad, researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
In the study, the researchers used kidney and adipose tissue biopsies from patients with diabetic kidney disease and healthy patients. They measured the levels of VEGF-B and lipid accumulation in the kidney and examined how these two parameters correlated with kidney function. Furthermore, the collected data were validated by extracting information on gene expression from RNA-seq databases in patients with diabetic kidney damage. As additional proof of concept, genetically modified mice were used to study the role of VEGF-B in fat release from white adipose tissue, increased fat uptake in the kidney, and the induced kidney damage.
"We are now working further to understand the mechanisms behind how VEGF-B and other vascular growth factors regulate the release of fatty acids from white adipose tissue, and how dysregulation of this process contributes to systemic lipotoxicity and the development of other diabetic complications," says Annelie Falkevall, corresponding author of the study and researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
The study is the result of a collaboration with other researchers at Karolinska Institutet, as well as researchers at the Sahlgrenska Academy, University of Gothenburg.
The study was funded by: the Swedish Research Council, the Swedish Cancer Society, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the European Foundation for the Study of Diabetes, CSL Innovation Pty Ltd., and Karolinska Institutet.
Publication
Folestad E, Mehlem A, Ning FC, Oosterveld T, Palombo I, Singh J, Olauson H, Witasp A, Thorell A, Stenvinkel P, Ebefors K, Nyström J, Eriksson U, Falkevall A
Kidney Int 2024 Dec;():
