2. Academic Validation
  3. Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis

  • Mol Metab. 2023 Feb 24;101698. doi: 10.1016/j.molmet.2023.101698.
Qiongyu Lu 1,  Ziting Liu 1,  Luyao Zhao 1,  Linru Xu 1,  Chu Liu 1,  Ling Li 1,  Yiren Cao 1,  Fengchan Li 1,  Lili Wu 1,  Lei Wang 1,  Ting Chen 1,  Tao You 1,  Lijie Ren 1,  Guixue Wang 2,  Chaojun Tang 3,  Li Zhu 4
Affiliations

Affiliations

  • 1 Cyrus Tang Medical Institute, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology of Jiangsu Province, Suzhou Key Lab of Thrombosis and Hemostasis, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.
  • 2 JinFeng Laboratory, Chongqing, China; Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China.
  • 3 Cyrus Tang Medical Institute, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology of Jiangsu Province, Suzhou Key Lab of Thrombosis and Hemostasis, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China; National Clinical Research Center for Hematologic Diseases at the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; The Ninth Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China; JinFeng Laboratory, Chongqing, China. Electronic address: zjtang@suda.edu.cn.
  • 4 Cyrus Tang Medical Institute, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology of Jiangsu Province, Suzhou Key Lab of Thrombosis and Hemostasis, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China; National Clinical Research Center for Hematologic Diseases at the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; The Ninth Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China; JinFeng Laboratory, Chongqing, China. Electronic address: zhul@suda.edu.cn.
PMID: 36842496 DOI: 10.1016/j.molmet.2023.101698
Abstract

Objective: Obesity and related diseases are becoming a growing risk for public health around the world due to the westernized lifestyle. Sema7A, an axonal guidance molecule, has been known to play a role in neurite growth, bone formation, and immune regulation. Whether Sema7A participates in obesity and metabolic diseases is unknown. As several SNPs in SEMA7A and its receptors were found to correlate with BMI and metabolic parameters in the human population, we investigated the potential role of Sema7A in obesity and hepatic steatosis.

Methods: GWAS and GEPIA database was used to analyze SNPs in SEMA7A and the correlation of Sema7A expression with lipid metabolism related genes. Sema7A-/- mice and recombinant Sema7A (rSema7A) were used to study the role of Sema7A in HFD-induced obesity and hepatic steatosis. Adipose tissue-derived mesenchymal stem cells (ADSCs) were used to examine the role of Sema7A in adipogenesis, lipogenesis and downstream signaling.

Results: Deletion of Sema7A aggravated HFD-induced obesity. Sema7A deletion enhanced adipogenesis in both subcutaneous and visceral ADSCs, while the addition of rSema7A inhibited adipogenesis of ADSCs and lipogenesis of differentiated mature adipocytes. Sema7A inhibits adipo/lipogenesis potentially through its receptor Integrin β1 and downstream FAK signaling. Importantly, administration of rSema7A had protective effects against diet-induced obesity in mice. In addition, deletion of Sema7A led to increased hepatic steatosis and Insulin resistance in mice.

Conclusions: Our findings reveal a novel inhibitory role of Sema7A in obesity and hepatic steatosis, providing a potential new therapeutic target for obesity and metabolic diseases.

Keywords

ADSCs; Adipogenesis; Hepatic steatosis; Lipogenesis; Obesity; Sema7A.

Figures
Products