Liraglutide Mitigates Renal Injury in Diabetic Kidney Disease by Suppressing Podocyte Cholesterol Accumulation Through mTOR / VMP1 ‐Regulated Autophagy

Nov 17, 2025FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Liraglutide may reduce kidney damage in diabetic disease by lowering cholesterol buildup in kidney filtering cells through a cell cleanup process controlled by mTOR and VMP1

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Liraglutide significantly reduces fasting blood glucose, low-density lipoprotein cholesterol, triglycerides, and total cholesterol while increasing high-density lipoprotein cholesterol levels in diabetic kidney disease rats.

Liraglutide is associated with decreased renal damage in diabetic kidney disease models.
Autophagy activity may be enhanced by liraglutide, which is linked to improved cholesterol transport.
Liraglutide upregulates the expression of ABCA1, potentially alleviating cholesterol accumulation in the kidneys.
Both in vivo and in vitro findings indicate that liraglutide reduces podocyte cholesterol accumulation.
The reduction of cholesterol accumulation in podocytes is mediated through the mTOR/VMP1 pathway.

AI simplified

Diabetic kidney disease (DKD) is seriously threatening the health of hundreds of millions of diabetes patients worldwide. Research has revealed that liraglutide attenuates renal damage in DKD rats by upregulating autophagic activity. Moreover, autophagy activity can affect cholesterol transport. Nevertheless, it is unclear whether liraglutide improves cholesterol accumulation in DKD rats by regulating autophagy. The DKD model was constructed by performing unilateral nephrectomy on high-fat diet (HFD) rats, followed by intraperitoneal injection of streptozotocin (STZ). The fasting blood glucose (FBG), albumin (ALB), creatinine (Cr), cholesterol, and triglyceride (TG) were measured by kits. The pathological changes in rat kidneys were observed through hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. An in vitro model of DKD was established by exposing podocytes to high glucose. The levels of Nephrin and Podocin in the kidneys or podocytes were measured by immunofluorescence. Filipin III staining was used to measure the cholesterol accumulation. The protein levels of microtubule-associated protein 1 light chain 3 (LC3), P62, Beclin-1, mammalian target of rapamycin (mTOR), vacuole membrane protein 1 (VMP1), and ATP-binding cassette transporter A1 (ABCA1) were assessed by western blot. Liraglutide demonstrated significant efficacy in mitigating hyperglycemia and modulating dyslipidemia in DKD rats, evidenced by marked reductions in FBG, low-density lipoprotein cholesterol (LDL-C), TG, and total cholesterol (Tch), while concurrently elevating high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, liraglutide promotes autophagy. Additionally, liraglutide upregulates the expression of ABCA1, which alleviates cholesterol accumulation in the kidneys of DKD rats. Both in vivo and in vitro studies have confirmed that liraglutide reduces podocyte cholesterol accumulation in DKD by enhancing autophagy through the mTOR/VMP1 pathway. Liraglutide reduces podocyte cholesterol accumulation through mTOR/VMP1-mediated autophagy, thereby alleviating renal injury in DKD.

Full Text

Full text is available at the source.

View full text ↗

Liraglutide Mitigates Renal Injury in Diabetic Kidney Disease by Suppressing Podocyte Cholesterol Accumulation Through mTOR / VMP1 ‐Regulated Autophagy

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief