Buzelle Samyra L, MacPherson Rebecca E K, Peppler Willem T, Castellani Laura, Wright David C
Department of Biochemistry, Ribeirao Preto Medical School, University of Sao Paulo, Riberao Preto, Brazil.
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Physiol Rep. 2015 Feb 22;3(2). doi: 10.14814/phy2.12312. Print 2015 Feb 1.
The chronic activation of beta 3 adrenergic receptors results in marked alterations in adipose tissue morphology and metabolism, including increases in mitochondrial content and the expression of enzymes involved in lipogenesis and glyceroneogenesis. Acute treatment with CL 316,243, a beta 3 adrenergic agonist, induces the expression of interleukin 6. Interestingly, IL-6 has been shown to induce mitochondrial genes in cultured adipocytes. Therefore, the purpose of this paper was to examine the role of interleukin 6 in mediating the in vivo effects of CL 316,243 in white adipose tissue. Circulating IL-6, and markers of IL-6 signaling in white adipose tissue were increased 4 h following a single injection of CL 316,243 in C57BL6/J mice. Once daily injections of CL 316,243 for 5 days increased the protein content of a number of mitochondrial proteins including CORE1, Cytochrome C, PDH, MCAD, and Citrate Synthase to a similar extent in adipose tissue from WT and IL-6(-/-) mice. Conversely, CL 316,243-induced increases in COXIV and phosphorylated AMPK were attenuated in IL-6(-/-) mice. Likewise, the slight, but significant, CL 316,243-induced increases in ATGL, PEPCK, and PPARγ, were reduced or absent in adipose tissue IL-6(-/-) mice. The attenuated response to CL 316,243 in white adipose tissue in IL-6(-/-) mice was associated with reductions in whole-body oxygen consumption and energy expenditure in the light phase. Our findings suggest that IL-6 plays a limited role in CL 316,243-mediated adipose tissue remodeling.
β3肾上腺素能受体的慢性激活会导致脂肪组织形态和代谢发生显著改变，包括线粒体含量增加以及参与脂肪生成和甘油生成的酶的表达增加。用β3肾上腺素能激动剂CL 316,243进行急性处理可诱导白细胞介素6的表达。有趣的是，白细胞介素6已被证明可在培养的脂肪细胞中诱导线粒体基因的表达。因此，本文的目的是研究白细胞介素6在介导CL 316,243对白色脂肪组织的体内作用中的作用。在C57BL6/J小鼠单次注射CL 316,243后4小时，循环中的白细胞介素6以及白色脂肪组织中白细胞介素6信号的标志物增加。每天注射一次CL 316,243，连续注射5天，WT和IL-6(-/-)小鼠脂肪组织中线粒体蛋白CORE1、细胞色素C、丙酮酸脱氢酶、中链酰基辅酶A脱氢酶和柠檬酸合酶的蛋白含量增加程度相似。相反，在IL-6(-/-)小鼠中，CL 316,243诱导的COXIV和磷酸化AMPK的增加减弱。同样，在脂肪组织IL-6(-/-)小鼠中，CL 316,243诱导的ATGL、磷酸烯醇式丙酮酸羧激酶和PPARγ的轻微但显著的增加减少或消失。IL-6(-/-)小鼠白色脂肪组织对CL 316,243的反应减弱与光期全身耗氧量和能量消耗的减少有关。我们的研究结果表明，白细胞介素6在CL 316,243介导的脂肪组织重塑中起有限作用。
