ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome
Abstract Background It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS developm...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-022-01632-y |
| _version_ | 1828378565357338624 |
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| author | Fu Zhong Shurao Liu Yue Li Guanyu Li Ming Liu Jingzhi Wang Weijing Cui Yanhong Suo Xia Gao |
| author_facet | Fu Zhong Shurao Liu Yue Li Guanyu Li Ming Liu Jingzhi Wang Weijing Cui Yanhong Suo Xia Gao |
| author_sort | Fu Zhong |
| collection | DOAJ |
| description | Abstract Background It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. Methods We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. Results Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. Conclusions ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS. |
| first_indexed | 2024-04-14T08:28:44Z |
| format | Article |
| id | doaj.art-3fe42657989b4514bf55239beeaa5761 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-14T08:28:44Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-3fe42657989b4514bf55239beeaa57612022-12-22T02:03:58ZengBMCLipids in Health and Disease1476-511X2022-04-0121111310.1186/s12944-022-01632-yANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndromeFu Zhong0Shurao Liu1Yue Li2Guanyu Li3Ming Liu4Jingzhi Wang5Weijing Cui6Yanhong Suo7Xia Gao8Nephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityPediatric Intensive Care Unit Department, The First People’s Hospital of ZhaoqingNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s medical centerNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityPediatric Department, Gansu Provincial HospitalPediatric Department, Gansu Provincial HospitalNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract Background It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. Methods We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. Results Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. Conclusions ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.https://doi.org/10.1186/s12944-022-01632-yANGPTL3HyperlipidemiaProteinuriaNephrotic syndrome |
| spellingShingle | Fu Zhong Shurao Liu Yue Li Guanyu Li Ming Liu Jingzhi Wang Weijing Cui Yanhong Suo Xia Gao ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome Lipids in Health and Disease ANGPTL3 Hyperlipidemia Proteinuria Nephrotic syndrome |
| title | ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| title_full | ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| title_fullStr | ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| title_full_unstemmed | ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| title_short | ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| title_sort | angptl3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome |
| topic | ANGPTL3 Hyperlipidemia Proteinuria Nephrotic syndrome |
| url | https://doi.org/10.1186/s12944-022-01632-y |
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