加拿大科學(xué)家近日利用小鼠和人類肝臟細(xì)胞進(jìn)行的實(shí)驗(yàn)表明,，食用過(guò)多的果糖和葡萄糖會(huì)關(guān)閉調(diào)節(jié)睪丸激素和雌激素活性水平的基因，會(huì)使人容易患上多種疾病,，特別是女性,。這一發(fā)現(xiàn)鞏固了既往的健康飲食觀點(diǎn),，即多吃碳水化合物，少吃糖,。相關(guān)論文11月8日在線發(fā)表于《臨床檢查雜志》（Journal of Clinical Investigation）上,。
葡萄糖和果糖在肝臟中進(jìn)行代謝，當(dāng)食用過(guò)多的糖后,，肝臟就會(huì)將多余的糖轉(zhuǎn)化成油脂,。在最新的研究中，加拿大大不列顛哥倫比亞大學(xué)產(chǎn)科學(xué)與婦科醫(yī)學(xué)系的Geoffrey Hammond教授和研究小組利用小鼠和人類肝臟細(xì)胞進(jìn)行實(shí)驗(yàn),，結(jié)果發(fā)現(xiàn),，油脂含量的增加會(huì)關(guān)閉性激素綁定球蛋白（sex hormone binding globulin，簡(jiǎn)稱SHBG）基因,，從而降低血液中SHBG蛋白的含量,。
SHBG蛋白對(duì)于控制身體內(nèi)睪丸激素和雌激素的水平至關(guān)重要。如果缺乏SHBG蛋白,，那么身體就會(huì)產(chǎn)生更多的睪丸激素和雌激素,，會(huì)對(duì)身體造成傷害。對(duì)超重的女性來(lái)說(shuō),，表現(xiàn)為患痤瘡,、不育、多囊卵巢及子宮癌的風(fēng)險(xiǎn)增加,。另外,，SHBG反常的含量還會(huì)打亂雌激素和睪丸激素之間微妙的平衡，導(dǎo)致產(chǎn)生心血管疾病,，對(duì)女性來(lái)說(shuō)尤其如此,。
Hammond教授說(shuō)，“有了這個(gè)新的認(rèn)識(shí),，我們可以把SHBG作為一個(gè)生物標(biāo)記,，在癥狀出現(xiàn)之前就對(duì)肝臟功能進(jìn)行檢測(cè)。我們也可以用它來(lái)評(píng)估飲食干預(yù)和旨在提高肝臟代謝水平藥物的有效性,。”
此次發(fā)現(xiàn)還破除了之前的一種觀點(diǎn),，即認(rèn)為SHBG含量的降低是過(guò)量的胰島素所致。這一觀點(diǎn)是由臨床觀測(cè)而來(lái)——超重的前期糖尿病患者身體具有高含量的胰島素和低含量的SHBG,。此次研究證明,，罪魁禍?zhǔn)撞辉谝葝u素，而是肝臟對(duì)糖的代謝,。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
原始出處:
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: [email protected] .
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 (HNF-4) and replacement of HNF-4 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 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 and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4 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.
