2. Academic Validation
  3. RAB18 deficiency disrupts lipid metabolism and autophagy in mice

RAB18 deficiency disrupts lipid metabolism and autophagy in mice

  • Biochem Biophys Res Commun. 2025 May 26:760:151673. doi: 10.1016/j.bbrc.2025.151673.
Li-Wei Zhang 1,  Ya-Qi Han 2,  Yan Yang 3,  Yun-Jie Li 2,  Ying-Xian Ma 4,  Sheng-Li Ming 5
Affiliations

Affiliations

  • 1 School of Intelligent Finance and Accounting, Henan Vocational College of Agriculture, Zhengzhou, 451450, Henan Province, China. Electronic address: LiweiZhang202312@163.com.
  • 2 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China.
  • 3 Ningxia Shizuishan Second People's Hospital, Shizuishan, 753000, Ningxia, China.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China. Electronic address: 838543725@qq.com.
  • 5 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan Province, China. Electronic address: mingsl911102@163.com.
PMID: 40157288 DOI: 10.1016/j.bbrc.2025.151673
Abstract

Mutation of the small G protein member RAB18 can lead to Warburg Micro Syndrome, characterized clinically by visual impairment and hind limb weakness. However, the cellular and molecular functions of RAB18 in mice are not fully understood. We obtained 3 Rab18+/+ and 3 Rab18-/- mice by using CRISPR/Cas9 technology. Rab18-/- mice exhibit symptoms of ocular shrinkage and hind limb weakness, along with griping/curling when tail suspended. Through metabolomics analysis, we found that Rab18 knockout affects lipid, vitamin, and amino acid metabolism while also impacting the Autophagy signaling pathway. Lipid analysis of the mouse liver revealed that Rab18 knockout led to an increase in hepatic lipid droplets, promoted elevated TC and TG levels, and impaired fatty acid release. Interestingly, Rab18 knockout promoted the expression of lipogenic genes and proteins but did not affect the expression of lipolytic genes and proteins. Since lipophagy, involved in lipid droplet breakdown, plays a key role, we found that Rab18 knockout inhibited the expression of liver autophagy-related genes and proteins. In summary, our results suggest that Rab18 plays a role in Autophagy in mice, likely contributing to mechanisms of lipid accumulation.

Keywords

Autophagy; Lipid metabolism; Rab18.

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