Bursać Biljana N, Vasiljević Ana D, Nestorović Nataša M, Veličković Nataša A, Vojnović Milutinović Danijela D, Matić Gordana M, Djordjevic Ana D
Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
J Nutr Biochem. 2014 Apr;25(4):446-55. doi: 10.1016/j.jnutbio.2013.12.005. Epub 2014 Jan 15.
Fructose overconsumption has been involved in the genesis and progression of the metabolic syndrome. Hypothalamus and adipose tissue, major organs for control of food intake and energy metabolism, play crucial roles in metabolic homeostasis. We hypothesized that glucocorticoid signaling mediates the effects of a fructose-enriched diet on visceral adiposity by acting on neuropeptide Y (NPY) in the hypothalamus and altering adipogenic transcription factors in the visceral adipose tissue. We analyzed the effects of 9-week consumption of 60% fructose solution on dyslipidemia, insulin and leptin sensitivity, and adipose tissue histology in male Wistar rats. Glucocorticoid signaling was assessed in both hypothalamus and visceral adipose tissue, while the levels of peroxisome-proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1 (SREBP-1) and lipin-1, together with the levels of their target genes expression, were analyzed in the visceral adipose tissue. The results showed that long-term consumption of highly concentrated liquid fructose led to the development of visceral adiposity, elevated triglycerides and hypothalamic leptin resistance accompanied by stimulated glucocorticoid signaling and NPY mRNA elevation. Results from adipose tissue implied that fructose consumption shifted the balance between glucocorticoid receptor and adipogenic transcriptional factors (PPARγ, SREBP-1 and lipin-1) in favor of adipogenesis judged by distinctly separated populations of small adipocytes observed in this tissue. In summary, we propose that high-fructose-diet-induced alterations of glucocorticoid signaling in both hypothalamus and adipose tissue result in enhanced adipogenesis, possibly serving as an adaptation to energy excess in order to limit deposition of fat in nonadipose tissues.
果糖摄入过量与代谢综合征的发生和发展有关。下丘脑和脂肪组织是控制食物摄入和能量代谢的主要器官，在代谢稳态中起着关键作用。我们假设糖皮质激素信号通过作用于下丘脑的神经肽Y（NPY）并改变内脏脂肪组织中的脂肪生成转录因子，介导富含果糖的饮食对内脏肥胖的影响。我们分析了雄性Wistar大鼠饮用60%果糖溶液9周对血脂异常、胰岛素和瘦素敏感性以及脂肪组织组织学的影响。评估了下丘脑和内脏脂肪组织中的糖皮质激素信号，同时分析了内脏脂肪组织中过氧化物酶体增殖物激活受体γ（PPARγ）、固醇调节元件结合蛋白-1（SREBP-1）和脂联素-1的水平及其靶基因表达水平。结果表明，长期摄入高浓度液态果糖会导致内脏肥胖、甘油三酯升高和下丘脑瘦素抵抗，同时伴有糖皮质激素信号激活和NPY mRNA升高。脂肪组织的结果表明，果糖摄入改变了糖皮质激素受体与脂肪生成转录因子（PPARγ、SREBP-1和脂联素-1）之间的平衡，有利于脂肪生成，这可以通过该组织中观察到的明显分离的小脂肪细胞群体来判断。总之，我们认为高果糖饮食引起的下丘脑和脂肪组织中糖皮质激素信号的改变导致脂肪生成增强，这可能是对能量过剩的一种适应，以限制脂肪在非脂肪组织中的沉积。
