Oana Fumiki, Takeda Hiroo, Hayakawa Kohichi, Matsuzawa Akane, Akahane Satoshi, Isaji Masayuki, Akahane Masuo
Division of Discovery Research, Kissei Pharmaceutical Co Ltd, 4365-1, Hotaka, Nagano 399-8304, Japan.
Metabolism. 2005 Aug;54(8):995-1001. doi: 10.1016/j.metabol.2005.02.016.
Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and hyperlipidemia. The aim of this study was to examine the physiological difference concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker rats. We therefore measured plasma adiponectin level and analyzed adiponectin and adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined the tissue mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa) Zucker rats and lean Zucker rats, by measuring adiponectin release from these cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma agonist increased adiponectin release only from the brown adipocytes isolated from lean Zucker rats. It is the conclusive difference between obese (fa/fa) Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa) Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin level, and low expression of PPARs in BAT leads to less sensibility of adiponectin release from brown adipocytes to a PPAR gamma agonist in obese (fa/fa) Zucker rats.
肥胖（fa/fa） Zucker大鼠是一种自发性遗传肥胖模型，与瘦 Zucker大鼠相比，表现出食欲亢进、高胰岛素血症和高脂血症。本研究的目的是检查肥胖（fa/fa） Zucker大鼠与对照瘦 Zucker大鼠在脂联素方面的生理差异。因此，我们测量了血浆脂联素水平，并分析了腹膜后白色脂肪组织（RT WAT）、棕色脂肪组织（BAT）、肝脏和比目鱼肌中脂联素和脂联素受体1 mRNA的表达。我们还通过测量肥胖（fa/fa） Zucker大鼠和瘦 Zucker大鼠棕色脂肪细胞对PPARγ激动剂的脂联素表达敏感性，检测了过氧化物酶体增殖物激活受体α（PPARα）、PPARδ和PPARγ的组织mRNA表达。肥胖（fa/fa） Zucker大鼠的血浆脂联素水平显著高于瘦 Zucker大鼠。肥胖（fa/fa） Zucker大鼠RT WAT中的脂联素mRNA表达水平低于瘦 Zucker大鼠，但BAT中的表达水平更高。肥胖（fa/fa） Zucker大鼠的RT WAT、BAT和肝脏中的脂联素受体1表达水平低于瘦 Zucker大鼠。肥胖（fa/fa） Zucker大鼠BAT中PPARα、PPARδ和PPARγ的表达水平低于瘦 Zucker大鼠。此外，PPARγ激动剂仅增加了从瘦 Zucker大鼠分离的棕色脂肪细胞中的脂联素释放。肥胖（fa/fa） Zucker大鼠的血浆脂联素水平显著高于瘦 Zucker大鼠，这是肥胖（fa/fa） Zucker大鼠与瘦 Zucker大鼠之间的决定性差异。此外，我们还阐明，尽管肥胖（fa/fa） Zucker大鼠血浆脂联素水平较高，但其RT WAT、BAT和肝脏中脂联素受体1的mRNA表达水平较低，并且BAT中PPARs的低表达导致肥胖（fa/fa） Zucker大鼠棕色脂肪细胞对PPARγ激动剂的脂联素释放敏感性降低。
