Department of Nutrition and Biochemistry, Institute of Sports Medicine, Peking University Third Hospital, Beijing 100191, China.
Chin Med J (Engl). 2012 Mar;125(5):874-81.
Visfatin, a visceral fat-derived adipocytokine, plays a significant physiological function in lipid metabolism. However, the precise function of visfatin and its regulation by thyroid hormones are still unknown. This study observed the plasma visfatin concentrations in subjects with hyperthyroidism and hypothyroidism in vivo, and investigated the possible regulation mechanism between visfatin and tri-iodothyronine (T3) in vitro as a further interpretation.
The experiment in vivo included clinical subjects (57 patients with thyroid dysfunction and 29 euthyroid healthy volunteers) and an animal model (24 Wistar rats). All subjects were divided into hyperthyroidism, hypothyroidism and euthyroidism groups, with plasma thyroid hormones, thyrotropin, visfatin and triglyceride concentrations determined. Visfatin mRNA expression in visceral fat and liver of rats was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The experiment in vitro studied 3T3-L1 cells and visfatin mRNA expression under nine different T3 concentrations (0, 0.1, 0.25, 0.5, 1, 5, 10, 20, 100 nmol/L) using quantitative real-time RT-PCR.
Clinical subjects and animal models showed elevated plasma visfatin concentrations in the hyperthyroidism group (20.466 ng/ml (15.263, 26.795 ng/ml) and (1209.164±165.292) ng/L) and hypothyroidism group (12.457 ng/ml (11.115, 15.454 ng/ml) and (1205.425±109.200) ng/L) compared to euthyroidism group (6.891 ng/ml (5.888, 8.803 ng/ml) and (926.650±54.002) ng/L, P<0.001). For animal models, visfatin mRNA expression in visceral fat in the hyperthyroidism and hypothyroidism groups increased about 3.33-fold and 1.98-fold compared to the euthyroidism group (P<0.001), which was positively correlated with plasma visfatin concentrations (r=0.713, P<0.001). However, no significant group difference (P>0.05) and correlation (r=0.121, P=0.572) was found in the liver. T3 induced a remarkable increase of visfatin mRNA expression in 3T3-L1 cells at low concentrations (0-0.5 nmol/L T3) followed by a sharp decrease at higher concentrations (0.5-100 nmol/L T3), with an inflection point at 0.5 nmol/L T3.
Elevated circulating visfatin levels in subjects with hyperthyroidism and hypothyroidism are possibly due to an increase of visfatin mRNA expression in visceral fat, and a nonlinear regulation mechanism on visfatin mRNA expression under various T3 concentrations might be involved.
内脏脂肪来源的脂肪细胞因子内脂素在脂质代谢中发挥着重要的生理功能。然而，内脂素的确切功能及其受甲状腺激素的调节仍不清楚。本研究在体内观察了甲状腺功能亢进和甲状腺功能减退患者的血浆内脂素浓度，并在体外研究了内脂素与三碘甲状腺原氨酸（T3）之间可能的调节机制。
体内实验包括临床研究对象（57 例甲状腺功能障碍患者和 29 例甲状腺功能正常的健康志愿者）和动物模型（24 只 Wistar 大鼠）。所有研究对象均分为甲状腺功能亢进组、甲状腺功能减退组和甲状腺功能正常组，检测血浆甲状腺激素、促甲状腺激素、内脂素和甘油三酯浓度。采用实时定量逆转录聚合酶链反应（RT-PCR）检测大鼠内脏脂肪和肝脏中内脂素 mRNA 的表达。体外实验采用 3T3-L1 细胞，在 9 种不同 T3 浓度（0、0.1、0.25、0.5、1、5、10、20、100nmol/L）下研究内脂素 mRNA 的表达，采用实时定量 RT-PCR 进行检测。
临床研究对象和动物模型均显示甲状腺功能亢进组（20.466ng/ml（15.263，26.795ng/ml）和（1209.164±165.292）ng/L）和甲状腺功能减退组（12.457ng/ml（11.115，15.454ng/ml）和（1205.425±109.200）ng/L）患者的血浆内脂素浓度高于甲状腺功能正常组（6.891ng/ml（5.888，8.803ng/ml）和（926.650±54.002）ng/L，P<0.001）。对于动物模型，甲状腺功能亢进组和甲状腺功能减退组的内脏脂肪中内脂素 mRNA 的表达分别增加了约 3.33 倍和 1.98 倍，与甲状腺功能正常组相比差异有统计学意义（P<0.001），且与血浆内脂素浓度呈正相关（r=0.713，P<0.001）。然而，在肝脏中，各组间差异无统计学意义（P>0.05），且相关性（r=0.121，P=0.572）也无统计学意义。T3 在低浓度（0-0.5nmol/L T3）下对内脂素 mRNA 的表达有显著的诱导作用，随后在高浓度（0.5-100nmol/L T3）下急剧下降，在 0.5nmol/L T3 时出现拐点。
甲状腺功能亢进和甲状腺功能减退患者循环内脂素水平升高可能是由于内脏脂肪中内脂素 mRNA 表达增加所致，而不同 T3 浓度对内脂素 mRNA 表达的非线性调节机制可能参与其中。
