Exogenous natural EPA-enriched phosphatidylcholine and phosphatidylethanolamine ameliorate lipid accumulation and insulin resistance <i>via</i> activation of PPARα/γ in mice

Tian

et al. 2021

J. Agric. Food Chem.

Self Cite

Osteoblasts play a key role in bone remodeling. Recent studies have reported that some hypertrophic chondrocytes co-expressing collagen I(Col I) and collagen X (ColX) could directly transdifferentiate into osteoblasts during endochondral ossification. However, whether nutrition intervention is beneficial to this transformation to improve osteoporosis (OP) remains unknown. In this study, ovariectomy (OVX)-induced OP mice were orally administered with docosahexaenoic acid (DHA) in different molecular forms for 13 weeks. The results showed that both DHA-triglyceride (DHA-TG) and DHA-phosphatidylcholine (DHA-PC) increased the bone mineral density and bone mineral apposition rate in ovariectomized mice, while DHA-ethyl esters (DHA-EE) had little effect. Interestingly, we found that both DHA-PC and DHA-TG increased the height of the growth plate, mainly increasing the number of hypertrophic chondrocytes. Further investigation by simultaneously labeling ColX and ColI indicated that DHA-PC and DHA-TG promoted the number of chondrocyte-transdifferentiated osteoblasts in the growth plate close to the diaphysis, in which DHA-PC performed better than DHA-TG. Apoptosis was not the only fate of hypertrophic chondrocytes. Western blot results showed that both DHA-TG and DHA-PC downregulated the Bax and cleaved-caspase3 expression and upregulated Bcl-2 expression in the growth plate, suggesting that chondrocyte apoptosis is inhibited. Runx2, the key regulator of chondrocyte-to-osteoblast transdifferentiation, was significantly increased by DHA-TG and DHA-PC, while DHA-EE had no effect on the above indicators. To our best knowledge, this is the first report that both DHA-PC and DHA-TG enhanced bone formation via promoting the chondrocyte-to-osteoblast transdifferentiation in the growth plate, contributing to the amelioration of OP. These activities depend on the molecular forms of DHA and their bioavailabilities. Our results provide guidance for the application of fish oil for bone health.

Section: Discussionsupporting

confidence: 84%

Section: ■ Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative Study of DHA with Different Molecular Forms for Ameliorating Osteoporosis by Promoting Chondrocyte-to-Osteoblast Transdifferentiation in the Growth Plate of Ovariectomized Mice

Tian

et al. 2021

J. Agric. Food Chem.

Self Cite

“…A previous study found that dietary PC was mainly hydrolyzed to 1-lyso-PC, which was effectively absorbed and reacylated to PC or degraded to glycerophoshocholine GPC , glycerophosphate and free choline 35 . Although dietary EPA-PC and EPA-PE can change the composition of fatty acids in the blood 36 , the brain is a closed system isolated by the blood-brain barrier, and supplementation of exogenous lipids may not cause significant changes in the composition of brain lipids.…”

Section: Pufa Content In Glycerophospholipidsmentioning

confidence: 99%

Effects of Dietary Supplementation with EPA-enriched Phosphatidylcholine and Phosphatidylethanolamine on Glycerophospholipid Profile in Cerebral Cortex of SAMP8 Mice fed with High-fat Diet

et al. 2021

Self Cite

The destruction of lipid homeostasis is associated with nervous system diseases such as Alzheimer's disease (AD). It has been reported that dietary EPA-enriched phosphatidylcholine (EPA-PC) and phosphatidylethanolamine (EPA-PE) could improve brain function. However, it was unclear that whether EPA-PC and EPA-PE intervention could change the lipid composition of cerebral cortex in AD mice. All the senescence-accelerated mouse-prone 8 (SAMP8) mice were fed with a high-fat diet for 8 weeks. After another 8 weeks of intervention with EPA-PC and EPA-PE (1%, w/w), the cerebral cortex lipid levels were determined by lipidomics. Results demonstrated that dietary supplementation with EPA-PE and EPA-PC for 8 weeks significantly increased the amount of choline plasmalogen (pPC) and Lysophosphatidylethanolamine (LPE) in the cerebral cortex of SAMP8 mice fed with high fat diet. Meanwhile, administration with EPA-PE and EPA-PC could significantly decrease the level of docosapentaenoic acid (DPA)-containing phosphatidylserine (PS) as well as increase the levels of arachidonic acid (AA)-containing phosphatidylethanolamine and PS in cerebral cortex. EPA-PE and EPA-PC could restore the lipid homeostasis of dementia mice to a certain degree, which might provide a potential novel therapy strategy and direction of dietary intervention in patients with cognitive impairment.

J Biochem & Molecular Tox

Effects of ginsenoside Rh2 on cisplatin‐induced nephrotoxicity in renal tubular epithelial cells by inhibiting endoplasmic reticulum stress

Wang,

Hao,

et al. 2024

Nephrotoxicity remains a major adverse reaction of the anticancer drug cisplatin (CDDP) chemotherapy, which is an important risk factor for chronic renal disease. Ginsenoside Rh2 from Panax ginseng has been shown to protect against CDDP‐induced nephrotoxicity in vivo, but its pharmacological effect on renal tubular epithelial cells is not clearly understood. This study examined the molecular mechanisms underlying the nephroprotective effects of Rh2 on CDDP‐induced HK‐2 cells and acute kidney injury (AKI) mice. As a result of Rh2 treatment, CDDP‐induced HK‐2 cells showed increased cell viability and reduced lactate dehydrogenase release. Moreover, Rh2 ameliorated CDDP‐induced mitochondrial membrane potential, increased antioxidant enzyme activities, and reduced pro‐inflammatory cytokine expression to reduce damage. Rh2 inhibited apoptosis and enhanced the antioxidant capacity of HK‐2 cells by reducing proteins associated with endoplasmic reticulum (ER) stress, as well as by attenuating tunicamycin‐induced ER stress. In addition, treatment of CDDP‐induced AKI mice with Rh2 substantially reduced blood urea nitrogen and serum creatinine levels, attenuated histological damage of kidney. Further, Rh2 also improved kidney function by inhibiting ER stress to support in vitro findings. These results consistently demonstrated that Rh2 protects renal tubular epithelial cells from CDDP‐induced nephrotoxicity and apoptosis by restoring ER homeostasis, which might suggest a therapeutic potential and providing new insights into AKI alternative therapies.