Renoprotective and anti-inflammatory effects of growth differentiation factor 15 (GDF15) in mice with diet-induced obesity

Abstract

Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine studied recently for its role in multiple biological processes and diseases. This transforming growth factor beta (TGF-b) family member has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have focused on the role of GDF15 in the kidneys. In this study, we hypothesized that GDF15 ameliorates obesity-induced inflammation and fibrosis in the kidney. We treated wild-type (WT) and GDF15 transgenic (NAG) mice with high-fat diets (HFD) (42% calories from fat) or normal chow. Analysis of four groups of mice (WT, WT+HFD, NAG, and NAG+HFD) illustrated significantly reduced levels of kidney fibrosis (a-SMA, TGF-b) and inflammation (NFkB, TNF-a) in the NAG with HFD mice. The kidney injury markers NGAL and TIM-1 were significantly reduced in the NAG+HFD mice. We also found decreased urinary norepinephrine excretion and serum creatinine, and increased glomerular filtration rate, urine volume, and sodium excretion in GDF15 transgenic mice with HFD. Further, in vitro study showed that GDF15 treatment reduced norepinephrine-induced kidney fibrosis and pro-inflammatory cytokine production in cultured kidney HK-2 and LLC cells. These results suggest GDF15 is a possible therapeutic target for kidney injury via its anti-inflammatory and anti-fibrosis protective effects. Funded by NIH R01-DK-114663 & R01-DK-129311 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.