JCI：糖摄入过多尤其不利女性健康

佚名

    加拿大科学家近日利用小鼠和人类肝脏细胞进行的实验表明，食用过多的果糖和葡萄糖会关闭调节睾丸激素和雌激素活性水平的基因，会使人容易患上多种疾病，特别是女性。这一发现巩固了既往的健康饮食观点，即多吃碳水化合物，少吃糖。相关论文11月8日在线发表于《临床检查杂志》（Journal  of  Clinical  Investigation）上。

    葡萄糖和果糖在肝脏中进行代谢，当食用过多的糖后，肝脏就会将多余的糖转化成油脂。在最新的研究中，加拿大大不列颠哥伦比亚大学产科学与妇科医学系的Geoffrey  Hammond教授和研究小组利用小鼠和人类肝脏细胞进行实验，结果发现，油脂含量的增加会关闭性激素绑定球蛋白（sex  hormone  binding  globulin，简称SHBG）基因，从而降低血液中SHBG蛋白的含量。

    SHBG蛋白对于控制身体内睾丸激素和雌激素的水平至关重要。如果缺乏SHBG蛋白，那么身体就会产生更多的睾丸激素和雌激素，会对身体造成伤害。对超重的女性来说，表现为患痤疮、不育、多囊卵巢及子宫癌的风险增加。另外，SHBG反常的含量还会打乱雌激素和睾丸激素之间微妙的平衡，导致产生心血管疾病，对女性来说尤其如此。

Hammond教授说，“有了这个新的认识，我们可以把SHBG作为一个生物标记，在症状出现之前就对肝脏功能进行检测。我们也可以用它来评估饮食干预和旨在提高肝脏代谢水平药物的有效性。”

    此次发现还破除了之前的一种观点，即认为SHBG含量的降低是过量的胰岛素所致。这一观点是由临床观测而来——超重的前期糖尿病患者身体具有高含量的胰岛素和低含量的SHBG。此次研究证明，罪魁祸首不在胰岛素，而是肝脏对糖的代谢。（科学网  梅进/编译）

原始出处:

J. Clin. Invest. doi:10.1172/JCI32249.
Copyright ©2007 by the American Society for Clinical Investigation

Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene

David M. Selva1,2, Kevin N. Hogeveen2,3, Sheila M. Innis4 and Geoffrey L. Hammond1,2

1Department of Obstetrics and Gynecology, University of British Columbia, and Child and Family Research Institute, Vancouver, British Columbia, Canada. 2University of Western Ontario, London, Ontario, Canada. 3UMR-INSERM U449, Faculté de Médecine RTH Laënnec, Lyon, France. 4Department of Pediatrics, University of British Columbia, and Child and Family Research Institute, Vancouver, British Columbia, Canada.

Address correspondence to: Geoffrey L. Hammond, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada. Phone: (604) 875-2435; Fax: (604) 875-2496; E-mail: ghammond@cw.bc.ca .

Received for publication March 28, 2007, and accepted in revised form August 29, 2007.

The liver produces plasma sex hormone–binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. In overweight children and adults, low plasma SHBG levels are a biomarker of the metabolic syndrome and its associated pathologies. Here, we showed in transgenic mice and HepG2 hepatoblastoma cells that monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes. This occurred via a downregulation of hepatocyte nuclear factor–4 {alpha} (HNF-4 {alpha} ) and replacement of HNF-4 {alpha} by the chicken OVA upstream promoter–transcription factor 1 at a cis-element within the human SHBG promoter, coincident with repression of its transcriptional activity. The dose-dependent reduction of HNF-4 {alpha} levels in HepG2 cells after treatment with glucose or fructose occurred in concert with parallel increases in cellular palmitate levels and could be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition of lipogenesis prevented monosaccharide-induced downregulation of HNF-4 {alpha} and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4 {alpha} levels, which in turn attenuated SHBG expression. This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption.