Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

Laminaria japonica polysaccharide attenuates podocyte epithelial-mesenchymal transformation via TGF-ß1-mediated Smad3 and p38MAPK pathways.

In the present work, we explored the interventional effect and potential mechanism of a purified Laminaria japonica polysaccharide (LJP61A) on podocyte epithelial-mesenchymal transition (EMT) in TGF-ß1-induced podocytes and adriamycin-treated mice. Results showed that compared to the model groups, LJP61A significantly up-regulated the levels of epithelial markers (Nephrin, WT-1, podocin) and down-regulated the levels of mesenchymal markers (α-SMA, FN1) in vitro and in vivo, thus preventing EMT-like morphological changes of podocytes, proteinuria and kidney injury. Smad3 and p38MAPK are two central pathways mediating podocyte EMT activated by TGF-ß1. We found that LJP61A suppressed TGF-ß1-induced activation of Smad3, Smad4 and p38MAPK in vitro and in vivo. Moreover, the inhibitory actions of LJP61A on podocyte EMT were synergistically strengthened by Smad3 inhibitor SIS3 and p38MAPK inhibitor SB203580. Taken together, these findings revealed that LJP61A could prevent podocyte EMT, which might be related to the inhibition of TGF-ß1-mediated Smad3 and p38MAPK pathways.

Inhibition of Ca2+-calpain signaling is a new mechanism using Laminaria japonica polysaccharide to prevent macrophage foam cell formation and atherosclerosis.

The Ca2+-calpain signaling plays a pivotal role in regulating the upstream signaling pathway of cellular autophagy. The aim of the current work was to investigate the role of Ca2+-calpain signaling in the regulation of macrophage autophagy by a Laminaria japonica polysaccharide (LJP61A) in Ox-LDL induced macrophages and high fat diet fed atherosclerotic mice. Results revealed that the LJP61A markedly decreased the levels of intracellular Ca2+, calpain1, calpain2 and their downstream effectors (Gsα, cAMP and IP3), and simultaneously enhanced autophagy activity and lipid metabolism, thereby reducing lipid accumulation in the Ox-LDL stimulated macrophages and lipid-laden plaques in atherosclerotic mice. Moreover, BAPTA-AM (a Ca2+ chelator) and calpeptin (a calpain inhibitor) synergistically strengthened the beneficial effects of LJP61A on autophagy and lipid metabolism by decreasing the levels of intracellular Ca2+, calpain1, calpain2, and their downstream effectors (Gsα, cAMP and IP3) induced by Ox-LDL. These findings suggested that the LJP61A suppressed macrophage derived foam cell formation and atherosclerosis by modulating the Ca2+-calpain-mediated autophagy.