Hepatic TMEM30A deficiency disrupts lipid metabolism and liver regeneration through PPARα-ATGL pathway.

Authors

Yilin Zhou, Xulin Gan, Jianv Cheng, Ke Ren, Yu Guo, Aixue Zhang, Yishan Jin, Zhongyuan Ge, Jialuo Wang, Zhenyu Ju, Liyun Shi, Lingling Zhang, Leiming Liu

Published in

iScience. Volume 29. Issue 10. Pages 117662. Oct 16, 2026. Epub Sep 29, 2026.

Abstract

The lipid accumulation at early phase during liver regeneration is necessary process, its functional role and regulatory mechanisms remain unclear. Here, we investigated the role of TMEM30A, a β-subunit of P4-ATPases, in hepatic lipid homeostasis and regeneration. Tmem30a liver-specific knockout (LKO) mice and controls were fed a high-fat diet and subjected to two-thirds partial hepatectomy. TMEM30A deficiency led to hepatic steatosis, dyslipidemia, and impaired induction of key triglyceride degradation and PPARα pathway genes. Following hepatectomy, LKO mice exhibited increased mortality, severe liver injury, reduced hepatocyte proliferation, and downregulation of Cyclin B1, Cyclin D1, and Cyclin E1. The lipid accumulation was markedly exaggerated in LKO livers, primarily due to suppression of the PPARα-ATGL axis. Pharmacological activation of PPARα with Wy-14643 restored lipid metabolism, hepatocyte proliferation, and survival after surgery. These findings reveal that the PPARα-ATGL pathway functions as a crucial downstream axis of TMEM30A in coordinating lipid metabolism and regenerative capacity.

PMID:
42861412
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

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