Hepatic-portal leptin sensor regulates energy metabolism

肝门瘦素传感器调节能量代谢

• 批准号: 13670067
• 负责人: YOSHIMATSU Hironobu
• 金额: $ 2.3万
• 依托单位: OITA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670067/
• 关键词: hepatic-portal vein; leptin; feeding behavior; energy metabolism; brown adipose tissue; adiponectin; 神経ヒスタミン; 交換神経; 交感神経; 視床下部

Present study aimed to clarify the functional role of hepatic-portal, leptin sensor in regulation of energy metabolism. Hepatic-portal infusion of leptin at a dose of 1000 μg/rat suppressed 24-h cumulative food intake and increased activity of sympathetic nerve innervating brown adipose tissue (BAT). However, that treatment with small dosage of leptin did not affect food intake nor nerve activity. Administration of leptin into the hepatic-portal vein decreased mRNA expression of sterol regulatory element binding protein and its downstream enzymes related with lipogenesis. Administration of histamine into the third cerebroventricle induced c-fos expressions in the paraventricular nucleus and the arcuate nucleus. In extrahypothalamic regions, c-fos expression was observed in the hippocampus and the amygdala. Intra-peritoneal administration of adiponectin (1.5mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in agouti yellow (A^y/a) obese mice. In addition, adiponectin treatment increased mRNA expression of UCP1 mRNA in the BAT. Furthermore, peripheral administration of adiponectin (1.5mg/kg, one shot) increased BAT sympathetic nerve activity accompanied by an increase of body temperature. These above responses were not induced by central application of adiponectin (15μg/kg). In summary, present study indicate that hepatic-portal leptin sensor may regulate lipid metabolism in the liver, but adiponectin may regulate energy metabolism through action of its hepatic-portal sensor.

本研究旨在阐明肝门瘦素传感器在能量代谢调节中的功能作用。肝门静脉注射瘦素1000μg/只可抑制大鼠24小时的累积摄食量，增加支配棕色脂肪组织(BAT)的交感神经活动。然而，小剂量的瘦素治疗不会影响食物摄入量和神经活动。肝-门静脉注射瘦素可降低与脂肪生成相关的类固醇调节元件结合蛋白及其下游酶的mRNA表达。第三脑室注射组胺可诱导室旁核和弓状核c-fos表达。在下丘脑外区，c-fos在海马区和杏仁核有表达。腹膜注射脂联素(1.5 mg/kg，连续7天)可减轻黄鼠肥胖小鼠的体重增加和内脏脂肪增加。此外，脂联素处理增加了蝙蝠UCP1mRNA的表达。此外，外周注射脂联素(1.5 mg/kg，一次注射)可增加蝙蝠的交感神经活动，并伴随体温升高。中枢性应用脂联素(15μg/kg)不能引起上述反应。综上所述，目前的研究表明，肝门型瘦素传感器可能调节肝脏的脂代谢，而脂联素可能通过其肝门型传感器的作用来调节能量代谢。

项目成果

Tuda, K, Yoshimatsu, H., Nijima, A, Chiba, S., Sakata T.: "Hypothalamic histamine neurons activate lipolysis in rat adipose tissue"ExBiol.Med.. 227. 208-216 (2002)

Tuda, K, Yoshimatsu, H., Nijima, A, Chiba, S., Sakata T.：“下丘脑组胺神经元激活大鼠脂肪组织中的脂肪分解”ExBiol.Med.. 227. 208-216 (2002)

Hidaka, S., Yoshimatsu, H, Kondou, S., Tsuruta, Y., Oka, K, Noguchi, H, Okamoto, K, Sakino, H, Teshima, Y., Okeda, T., Sakata T.: "Chronic central leptin infusion restores hyperglycemia independently of food intake and insulin level in streptozotocin-indu

日高 S.、吉松 H、近藤 S.、鹤田 Y.、冈 K、野口 H、冈本 K、崎野 H、丰岛 Y.、桶田 T.、坂田 T.：“

Tsuruta Y, et al.: "Hyperleptinemia in A y /a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression"Am J Physiol Endocrinol Metab.. 282. E967-E973 (2002)

Tsuruta Y 等人：“A y /a 小鼠中的高瘦素血症上调弓形可卡因和安非他明调节的转录物表达”Am J Physiol Endocrinol Metab.. 282. E967-E973 (2002)

Yoshimatsu, H, Chiba, S., Tajima, D., Akehi, Y., Sakata, T.: "Histidine Suppresses Food Intake through Its Conversion into Neuronal Histamine"ExBiol.Med.. 227. 63-68 (2002)

Yoshimatsu, H, Chiba, S., Tajima, D., Akehi, Y., Sakata, T.：“组氨酸通过转化为神经元组胺来抑制食物摄入”ExBiol.Med.. 227. 63-68 (2002)

Tsuda K.: "Hypothalamic histamine neurons activate lipolysis in rat adipose tissue"Exp.Biol.Med.. (in press). (2002)

Tsuda K.：“下丘脑组胺神经元激活大鼠脂肪组织中的脂肪分解”Exp.Biol.Med..（出版中）。