New Synthesized Activating Transcription Factor 3 Inducer SW20.1 Suppresses Resistin-Induced Metabolic Syndrome

Author:

Tran Tu T.12ORCID,Huang Wei-Jan3ORCID,Lin Heng4,Chen Hsi-Hsien567ORCID

Affiliation:

1. International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

2. Department of Internal Medicine, Thai Nguyen University of Medicine and Pharmacy, Thai Nguyen 241-17, Vietnam

3. School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan

4. Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

5. TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 110, Taiwan

6. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

7. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan

Abstract

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (−2861/−2854 and −241/−234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipogenesis-related gene expression, hepatic steatosis, and serum resistin levels. Overall, SW20.1 exerts antiobesity effects by inhibiting resistin through the ATF3 pathway. Our study results indicate that SW20.1 is a promising therapeutic drug for diet-induced obesity.

Funder

Ministry of Science and Technology

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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