PMID- 37781121 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231003 IS - 2296-861X (Print) IS - 2296-861X (Electronic) IS - 2296-861X (Linking) VI - 10 DP - 2023 TI - Extracellular thiamine concentration influences thermogenic competency of differentiating neck area-derived human adipocytes. PG - 1207394 LID - 10.3389/fnut.2023.1207394 [doi] LID - 1207394 AB - INTRODUCTION: Brown adipose tissue (BAT) dissipates energy in the form of heat majorly via the mitochondrial uncoupling protein 1 (UCP1). The activation of BAT, which is enriched in the neck area and contains brown and beige adipocytes in humans, was considered as a potential therapeutic target to treat obesity. Therefore, finding novel agents that can stimulate the differentiation and recruitment of brown or beige thermogenic adipocytes are important subjects for investigation. The current study investigated how the availability of extracellular thiamine (vitamin B1), an essential cofactor of mitochondrial enzyme complexes that catalyze key steps in the catabolism of nutrients, affects the expression of thermogenic marker genes and proteins and subsequent functional parameters during ex vivo adipocyte differentiation. METHODS: We differentiated primary human adipogenic progenitors that were cultivated from subcutaneous (SC) or deep neck (DN) adipose tissues in the presence of gradually increasing thiamine concentrations during their 14-day differentiation program. mRNA and protein expression of thermogenic genes were analyzed by RT-qPCR and western blot, respectively. Cellular respiration including stimulated maximal and proton-leak respiration was measured by Seahorse analysis. RESULTS: Higher thiamine levels resulted in increased expression of thiamine transporter 1 and 2 both at mRNA and protein levels in human neck area-derived adipocytes. Gradually increasing concentrations of thiamine led to increased basal, cAMP-stimulated, and proton-leak respiration along with elevated mitochondrial biogenesis of the differentiated adipocytes. The extracellular thiamine availability during adipogenesis determined the expression levels of UCP1, PGC1a, CKMT2, and other browning-related genes and proteins in primary SC and DN-derived adipocytes in a concentration-dependent manner. Providing abundant amounts of thiamine further increased the thermogenic competency of the adipocytes. DISCUSSION: Case studies in humans reported that thiamine deficiency was found in patients with type 2 diabetes and obesity. Our study raises the possibility of a novel strategy with long-term thiamine supplementation, which can enhance the thermogenic competency of differentiating neck area-derived adipocytes for preventing or combating obesity. CI - Copyright (c) 2023 Vinnai, Arianti, Gyory, Bacso, Fesus and Kristof. FAU - Vinnai, Boglarka Agnes AU - Vinnai BA AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. AD - Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary. FAU - Arianti, Rini AU - Arianti R AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. AD - Universitas Muhammadiyah Bangka Belitung, Pangkalanbaru, Indonesia. FAU - Gyory, Ferenc AU - Gyory F AD - Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. FAU - Bacso, Zsolt AU - Bacso Z AD - Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary. AD - Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. AD - Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary. FAU - Fesus, Laszlo AU - Fesus L AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. FAU - Kristof, Endre AU - Kristof E AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. LA - eng PT - Journal Article DEP - 20230913 PL - Switzerland TA - Front Nutr JT - Frontiers in nutrition JID - 101642264 PMC - PMC10534038 OTO - NOTNLM OT - UCP1 OT - adipocytes OT - beige OT - obesity OT - thermogenesis OT - thiamine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/10/02 06:42 MHDA- 2023/10/02 06:43 PMCR- 2023/01/01 CRDT- 2023/10/02 04:39 PHST- 2023/04/17 00:00 [received] PHST- 2023/08/14 00:00 [accepted] PHST- 2023/10/02 06:43 [medline] PHST- 2023/10/02 06:42 [pubmed] PHST- 2023/10/02 04:39 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fnut.2023.1207394 [doi] PST - epublish SO - Front Nutr. 2023 Sep 13;10:1207394. doi: 10.3389/fnut.2023.1207394. eCollection 2023.