Ghorbani M, Himms-Hagen J
Department of Biochemistry, University of Ottawa, Canada.
Int J Obes Relat Metab Disord. 1998 Jan;22(1):63-5. doi: 10.1038/sj.ijo.0800544.
To assess the effect of chronic treatment with a beta 3-adrenoceptor agonist, CL 316,243 (CL) on serum leptin concentration in rats with diet-induced obesity (DIO) or with genetic obesity (fa/fa Zucker).
Leptin concentration was measured in serum of young control rats, young rats with DIO and old control or genetically obese fa/fa Zucker rats, that were treated chronically with CL for 2-4 weeks in our previous studies.
Treatment with CL reduced elevated leptin concentrations in young rats with DIO and in old mildly obese control rats to the low concentration of young lean rats. It did not alter the grossly elevated concentration in fa/fa rats. This effect of CL correlated well with its effect to reduce white adipocyte size, except in fa/fa rats. In CL-treated fa/fa rats, despite reductions in body fat mass and in white adipocyte size, and despite normalization of both hyperglycemia and hyperinsulinemia, the leptin concentration did not change.
The reason for lack of change in leptin concentrations in fa/fa rats, despite shrinking of white adipocytes and partial reversal of the obesity, may be due to another defect. The large increase in white adipocyte number in these animals was not reversed by the treatment and might have contributed to elevated leptin production. In addition, all forms of leptin receptor are known to be defective in fa/fa rats. Since leptin is rapidly excreted in urine and leptin receptors (including a form known to be involved in leptin transport) are expressed in the kidney, we suggest that leptin excretion is impaired in the fa/fa rat. This impairment contributes to maintenance of an elevated concentration of leptin in its blood and prevents treatment with a beta 3-adrenoceptor agonist from reducing this elevated concentration despite reversal of both obesity and diabetes. In addition, we suggest that CL-induced suppression of hyperphagia in fa/fa rats is leptin-independent and due to the large increase in thermogenesis.
评估用β3 - 肾上腺素能受体激动剂CL 316,243（CL）长期治疗对饮食诱导肥胖（DIO）大鼠或遗传性肥胖（fa/fa Zucker）大鼠血清瘦素浓度的影响。
在我们之前的研究中，对年轻对照大鼠、患有DIO的年轻大鼠以及年老对照或遗传性肥胖的fa/fa Zucker大鼠的血清瘦素浓度进行了测量，这些大鼠用CL长期治疗2 - 4周。
用CL治疗可将患有DIO的年轻大鼠和年老轻度肥胖对照大鼠中升高的瘦素浓度降低至年轻瘦大鼠的低浓度。它并未改变fa/fa大鼠中严重升高的浓度。CL的这种作用与其减少白色脂肪细胞大小的作用密切相关，但fa/fa大鼠除外。在经CL治疗的fa/fa大鼠中，尽管体脂量和白色脂肪细胞大小减少，且高血糖和高胰岛素血症均恢复正常，但瘦素浓度并未改变。
尽管白色脂肪细胞缩小且肥胖部分逆转，但fa/fa大鼠瘦素浓度缺乏变化的原因可能是由于另一种缺陷。这些动物白色脂肪细胞数量的大幅增加并未因治疗而逆转，这可能导致瘦素产生增加。此外，已知fa/fa大鼠中所有形式的瘦素受体均有缺陷。由于瘦素在尿液中迅速排泄，且瘦素受体（包括已知参与瘦素转运的一种形式）在肾脏中表达，我们认为fa/fa大鼠中瘦素排泄受损。这种损害有助于维持其血液中瘦素的高浓度，并且尽管肥胖和糖尿病均得到逆转，但用β3 - 肾上腺素能受体激动剂治疗仍无法降低这种升高的浓度。此外，我们认为CL诱导的fa/fa大鼠食欲亢进的抑制与瘦素无关，而是由于产热大幅增加。
