Fam Barbara C, Sgambellone Rebecca, Ruan Zheng, Proietto Joseph, Andrikopoulos Sofianos
Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia.
Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
J Endocrinol. 2015 Jun;225(3):191-204. doi: 10.1530/JOE-15-0131. Epub 2015 May 1.
Obesity susceptibility in humans and in rodent strains varies in response to the consumption of high-energy density (HED) diets. However, the exact mechanism(s) involved in this susceptibility remain(s) unresolved. The aim of the present study was to gain greater insight into this susceptibility by using C57BL/6J (B6) mice that were separated into obesity-prone (diet-induced obese (DIO)) and obesity-resistant (diet-induced resistant (DR)) groups following an HED diet for 6 weeks. Physiological, biochemical and gene expression assessments of energy balance were performed in the DIO and DR mice on an HED diet and chow-fed mice. The increased weight gain of the DIO mice as compared to the DR mice was associated with increased energy intake and higher plasma leptin and adiponectin levels but not with reduced physical activity or resting energy expenditure. Hypothalamic Pomc gene expression was elevated, but there were no changes in Npy or Agrp expression. Adipose tissue leptin and adiponectin gene expression were significantly reduced in the DIO group as compared to the DR group. Interestingly, ileum expression of G protein-coupled receptor (Gpr) 40 (Gpr40) was significantly increased, whereas Gpr120, Gpr119, Gpr41, and glucagon-like peptide 1 (Glp1) were reduced. Contrastingly, the lower weight gain of the DR group was associated with elevated adipose tissue leptin and adiponectin gene expression, but there were no differences in plasma hormone or hypothalamic gene expression levels as compared to chow-fed mice. Therefore, the present data demonstrate that susceptibility and resistance to diet-induced weight gain in B6 mice appears to be predominantly driven by peripheral rather than hypothalamic modifications, and changes in gut-specific receptors are a potentially important contributor to this variation.
人类和啮齿动物品系的肥胖易感性会因高能量密度（HED）饮食的摄入而有所不同。然而，这种易感性所涉及的确切机制仍未得到解决。本研究的目的是通过使用C57BL/6J（B6）小鼠来更深入地了解这种易感性，这些小鼠在接受HED饮食6周后被分为肥胖易感组（饮食诱导肥胖（DIO）组）和肥胖抵抗组（饮食诱导抵抗（DR）组）。对食用HED饮食的DIO和DR小鼠以及喂食普通饲料的小鼠进行了能量平衡的生理、生化和基因表达评估。与DR小鼠相比，DIO小鼠体重增加更多，这与能量摄入增加、血浆瘦素和脂联素水平升高有关，但与身体活动减少或静息能量消耗无关。下丘脑促黑素原（Pomc）基因表达升高，但神经肽Y（Npy）或刺鼠肽基因相关蛋白（Agrp）表达没有变化。与DR组相比，DIO组脂肪组织瘦素和脂联素基因表达显著降低。有趣的是，回肠中G蛋白偶联受体（Gpr）40（Gpr40）的表达显著增加，而Gpr120、Gpr119、Gpr41和胰高血糖素样肽1（Glp1）则减少。相反，DR组体重增加较少与脂肪组织瘦素和脂联素基因表达升高有关，但与喂食普通饲料的小鼠相比，血浆激素或下丘脑基因表达水平没有差异。因此，目前的数据表明，B型小鼠对饮食诱导体重增加的易感性和抗性似乎主要由外周而非下丘脑的改变驱动，肠道特异性受体的变化是这种差异的一个潜在重要因素。
