Affiliation:
1. Independent Researcher, 1000 Sofia, Bulgaria
2. Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria
3. Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
Abstract
Obesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed that the natural pterocarpan, maackiain (MACK), significantly inhibits adipogenic differentiation in human adipocytes through a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Considering the observed anti-adipogenic potential of MACK, we aimed to further elucidate the molecular mechanisms that drive its biological activity in a Caenorhabditis elegans obesity model. Therefore, in the current study, the anti-obesogenic effect of MACK (25, 50, and 100 μM) was compared to orlistat (ORST, 12 μM) as a reference drug. Additionally, the hybrid combination between the ORST (12 μM) and MACK (100 μM) was assessed for suspected synergistic interaction. Mechanistically, the observed anti-obesogenic effect of MACK was mediated through the upregulation of the key metabolic regulators, namely, the nuclear hormone receptor 49 (nhr-49) that is a functional homologue of the mammalian PPARs and the AMP-activated protein kinase (aak-2/AMPK) in C. elegans. Collectively, our investigation indicates that MACK has the potential to limit lipid accumulation and control obesity that deserves future developments.
Funder
European Union’s Horizon 2020 research and innovation programme
European Regional Development Fund
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference58 articles.
1. Signaling pathways in obesity: Mechanisms and therapeutic interventions;Wen;Signal Transduct. Target. Ther.,2022
2. Anti-obesity drug discovery: Advances and challenges;Muller;Nat. Rev. Drug Discov.,2022
3. DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity;Baca;Nutr. Diabetes,2022
4. Bourebaba, Y., Marycz, K., Mularczyk, M., and Bourebaba, L. (2022). Postbiotics as potential new therapeutic agents for metabolic disorders management. Biomed. Pharmacother., 123.
5. Intermittent and periodic fasting, longevity and disease;Longo;Nat. Aging,2021