Department of Cellular Regenerative Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.
Sci Rep. 2024 Aug 6;14(1):18252. doi: 10.1038/s41598-024-69364-w.
Brown fat is a therapeutic target for the treatment of obesity-associated metabolic diseases. However, nutritional intervention strategies for increasing the mass and activity of human brown adipocytes have not yet been established. To identify vitamins required for brown adipogenesis and adipocyte browning, chemical compound-induced brown adipocytes (ciBAs) were converted from human dermal fibroblasts under serum-free and vitamin-free conditions. Choline was found to be essential for adipogenesis. Additional treatment with pantothenic acid (PA) provided choline-induced immature adipocytes with browning properties and metabolic maturation, including uncoupling protein 1 (UCP1) expression, lipolysis, and mitochondrial respiration. However, treatment with high PA concentrations attenuated these effects along with decreased glycolysis. Transcriptome analysis showed that a low PA concentration activated metabolic genes, including the futile creatine cycle-related thermogenic genes, which was reversed by a high PA concentration. Riboflavin treatment suppressed thermogenic gene expression and increased lipolysis, implying a metabolic pathway different from that of PA. Thiamine treatment slightly activated thermogenic genes along with decreased glycolysis. In summary, our results suggest that specific B vitamins and choline are uniquely involved in the regulation of adipocyte browning via cellular energy metabolism in a concentration-dependent manner.
棕色脂肪是治疗肥胖相关代谢疾病的一个有潜力的治疗靶点。然而,增加人类棕色脂肪细胞数量和活性的营养干预策略尚未建立。为了鉴定棕色脂肪生成和脂肪细胞棕色化所必需的维生素,我们在无血清和无维生素的条件下,将人真皮成纤维细胞诱导为化学化合物诱导的棕色脂肪细胞(ciBAs)。结果发现胆碱对于脂肪生成是必需的。用泛酸(PA)处理可以赋予胆碱诱导的不成熟脂肪细胞棕色化特性和代谢成熟特性,包括解偶联蛋白 1(UCP1)的表达、脂肪分解和线粒体呼吸。然而,高浓度的 PA 处理会减弱这些作用,同时降低糖酵解。转录组分析表明,低浓度的 PA 激活了代谢基因,包括无效的肌酸循环相关的产热基因,而高浓度的 PA 则会逆转这种作用。核黄素处理会抑制产热基因的表达并增加脂肪分解,表明其代谢途径与 PA 不同。硫胺素处理会轻微激活产热基因,同时降低糖酵解。总之,我们的结果表明,特定的 B 族维生素和胆碱通过细胞能量代谢以浓度依赖的方式独特地参与调节脂肪细胞棕色化。