Title:Dysregulation of Angiopoietin-like-4 Associated with Hyperlipidemia-induced
Renal Injury by AMPK/ACC Pathway
Volume: 29
Issue: 4
Author(s): Wenhui Qiu, Luyang Huang, YueQiang Li, Qingquan Liu*YongMan Lv*
Affiliation:
- Department of Nephrology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095,
Jie Fang Avenue, Wuhan, 430030, China
- Department of Nephrology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095,
Jie Fang Avenue, Wuhan, 430030, China
- Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,
No. 1095, Jie Fang Avenue, Wuhan, 430030, China
Keywords:
Hyperlipidemia, dyslipidemia, Angptl4, podocytes, AMPK, palmitic acid.
Abstract:
Background: Angiopoietin-like protein 4 (Angptl4) is a glycoprotein that is involved in regulating
lipid metabolism, which has been indicated as a link between hypertriglyceridemia and albuminuria in glomerulonephropathy.
Deregulated lipid metabolism is increasingly recognized as an important risk factor of glomerulonephropathy.
This study aimed to investigate the Angptl4 expression in renal tissue and podocyte under hyperlipidemia
conditions and explore the potential molecular mechanisms.
Objective: The role of Angptl4 in hyperlipidemia-induced glomerular disease and the detailed underlying mechanisms
are unclear. This study sought new insights into this issue.
Methods: We measured Angptl4 levels in the plasma and urine from patients with hyperlipidemia and healthy
people. Rats were fed a high fat diet (HFD) to induce dyslipidemia model and the human podocytes were stimulated
by palmitic acid as in vivo and in vitro experiments. The podocytes injury and the Angptl4 level in renal
tissues were evaluated. Furthermore, the mechanism of Angptl4 on podocytes injury was investigated.
Results: The urinary Angptl4 level was gradually upregulated in both patients with hyperlipidaemia and high
fat-diet-induced rats. HFD rats showed increased 24 h urinary protein and glomerular tuft area at week 12. The
levels of nephrin and WT-1 were down-regulated, but the Angptl4 levels were markedly upregulated on the
glomerular of rats on HFD. In the human podocytes, lipid accumulation accompanied by increases of Angptl4,
but the expression of nephrin, WT-1, p-AMPKα and p-ACC was decreased after palmitic acid treatment. However,
this injury effect was mediated by the aminoimidazole-4-carboxamide-1β-D-ribofuranoside (AICAR), activator
of the low energy sensor AMPK/ACC signaling.
Conclusion: This study was the first of its kind to show that podocyte damage induced by dyslipidemia could
be associated with upregulated Angptl4 and that patients with hyperlipidemia might have relatively high urinary
Angptl4 expression. The dysregulation of Angptl4 in the podocytes under hyperlipidemia is possibly carried
out through AMPK/ACC signaling pathway.
