Böni-Schnetzler M, Hauri C, Zapf J
Department of Medicine, University Hospital, Zurich, Switzerland.
Diabetologia. 1999 Feb;42(2):160-6. doi: 10.1007/s001250051134.
To examine whether insulin-like growth factor I (IGF I) or growth hormone (GH) influences leptin in vivo we measured leptin mRNA in epididymal fat pads and serum leptin of normal rats infused subcutaneously for 6 days with recombinant human (rh)IGF I (1 mg/day), rhGH (200 mU/day), or vehicle. In addition, we determined fat pad weight and food consumption as well as IGF I, insulin, glucose, non-esterified fatty acid (NEFA), glycerol, beta-hydroxybutyrate and triglyceride (TG) serum concentrations. Food intake was identical during all three treatments. RhIGF I but not rhGH raised IGF I serum concentrations, reduced fat pad weight (60.3 +/- 7.4% of control rats, p = 0.019), and suppressed leptin mRNA (38.8 +/- 11.9% of control rats, p = 0.002), serum leptin (51.6 +/- 10.5% of control rats, p = 0.0028) and serum triglycerides (39.3 +/- 8.0% of control rats, p = 2.6 x 10(-6)). Both rhIGF I and rhGH reduced non-esterified fatty acids (NEFA) (p = 0.00001 and 0.0007, respectively), whereas serum glycerol, beta-OH butyrate and glucose concentrations remained unchanged. Serum insulin concentrations during rhIGF I were lower than during rhGH infusion and correlated with leptin mRNA (r = 0.589, p = 0.016) and fat pad weight (r = 0.643, p = 0.007). Reduction of adipose tissue mass and suppression of leptin by IGF I appear to be due to reduced circulating insulin leading to enhanced fat mobilization and NEFA oxidation as well as to increased gluconeogenesis from glycerol. In contrast, decreased NEFA concentrations during rhGH in the presence of unchanged fat pad weight, serum glycerol and triglycerides might result from more efficient re-esterification of released fatty acids within the triglyceride-fatty acid cycle. The results also show that exogenously infused IGF I and GH act on lipid metabolism by different mechanisms and suggest an IGF-independent, probably direct, metabolic effect of GH. Finally, in agreement with previous studies in GH-infused hypophysectomized rats, it appears unlikely that GH regulates leptin in the rat.
为了研究胰岛素样生长因子I（IGF I）或生长激素（GH）在体内是否影响瘦素，我们对正常大鼠皮下注射重组人（rh）IGF I（1毫克/天）、rhGH（200毫单位/天）或赋形剂6天，然后测量附睾脂肪垫中的瘦素mRNA和血清瘦素水平。此外，我们还测定了脂肪垫重量、食物摄入量以及血清中IGF I、胰岛素、葡萄糖、非酯化脂肪酸（NEFA）、甘油、β-羟基丁酸酯和甘油三酯（TG）的浓度。在所有三种治疗过程中，食物摄入量相同。rhIGF I而非rhGH提高了血清IGF I浓度，降低了脂肪垫重量（为对照大鼠的60.3±7.4%，p = 0.019），并抑制了瘦素mRNA（为对照大鼠的38.8±11.9%，p = 0.002）、血清瘦素（为对照大鼠的51.6±10.5%，p = 0.0028）和血清甘油三酯（为对照大鼠的39.3±8.0%，p = 2.6×10⁻⁶）。rhIGF I和rhGH均降低了非酯化脂肪酸（NEFA）（分别为p = 0.00001和0.0007），而血清甘油、β-羟基丁酸酯和葡萄糖浓度保持不变。rhIGF I治疗期间的血清胰岛素浓度低于rhGH输注期间，且与瘦素mRNA（r = 0.589，p = 0.016）和脂肪垫重量（r = 0.643，p = 0.007）相关。IGF I导致脂肪组织质量减少和瘦素受到抑制，似乎是由于循环胰岛素减少，从而导致脂肪动员和NEFA氧化增强，以及甘油的糖异生增加。相比之下，在脂肪垫重量、血清甘油和甘油三酯不变的情况下，rhGH治疗期间NEFA浓度降低，可能是由于在甘油三酯 - 脂肪酸循环中释放的脂肪酸再酯化效率更高。结果还表明，外源性注入的IGF I和GH通过不同机制作用于脂质代谢，并提示GH存在不依赖IGF的、可能直接的代谢作用。最后，与先前对注射GH的垂体切除大鼠的研究一致，GH似乎不太可能在大鼠中调节瘦素。
