Supplementary Material for: Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol-Binding Protein 4 Gene

Background/Aims: Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. Methods: This was a cross-sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their RBP4 variant. Results: Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the RBP4 variant. The T allele promoted adiposity-reducing effects of vitamin A in VF and adiposity-enhancing effects in SF, while the C allele had adiposity-reducing effects in both VF and SF. Conclusions: Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity.

背景与目的：内脏脂肪（Visceral fat, VF）相较皮下脂肪（Subcutaneous fat, SF）与心血管代谢疾病的关联更为紧密。膳食维生素A（retinol）或可通过对内脏脂肪与皮下脂肪的脂肪生成产生差异化调控作用以减少体脂堆积，且该效应的发挥受视黄醇结合蛋白4（retinol-binding protein-4, RBP4）调节。本研究旨在探讨膳食维生素A摄入与内脏脂肪、皮下脂肪是否存在关联，以及该关联是否受此前被证实与循环视黄醇水平相关的RBP4基因型（rs10882272，C/T）所调节。
方法：本研究为一项横断面关联研究，纳入来自法裔加拿大奠基者人群的947名青少年作为研究样本。采用磁共振成像量化内脏脂肪与皮下脂肪含量，通过24小时膳食回顾法评估膳食维生素A摄入情况，同时对所有参与者进行基因分型以确定其携带的RBP4变异类型。
结果：膳食维生素A摄入与内脏脂肪呈负相关，但与皮下脂肪无显著关联。上述关联不受年龄、性别、身高及能量摄入的混杂因素影响，且受RBP4变异体的调控。其中T等位基因可增强维生素A对内脏脂肪的减脂作用，同时强化其对皮下脂肪的增脂效应；而C等位基因则可同时减少内脏脂肪与皮下脂肪的堆积。
结论：膳食维生素A或可在青春期减少腹部体脂堆积，并以RBP4依赖的方式促进内脏脂肪向皮下脂肪的体脂重分布。本项观察性研究结果为未来干预性研究提供了理论依据，结合遗传信息的后续研究可进一步明确膳食维生素A摄入与腹部体脂堆积之间关联的因果关系。