Susceptibility to obesity and gallbladder stasis produced by a protein- and fat-enriched diet in male mice compared with female mice
Susceptibility to obesity and gallbladder stasis produced by a protein- and fat-enriched diet in male mice compared with female mice
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DOI：
10.1186/1743-7075-4-14
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发表时间：
2007-06-05
影响因子：
4.5
通讯作者：
Funakoshi, Akihiro
中科院分区：
文献类型：
--
作者：
Miyasaka, Kyoko;Kanai, Setsuko;Funakoshi, Akihiro
背景：20岁以上日本受试者中，男性代谢综合征的发生率为45.6%，而女性仅为16.7%。日本男性受试者比女性更易患代谢综合征的原因尚不清楚。一种可能性是日本男性受试者（40-70岁）有饮酒习惯的频率较高（67%），而女性受试者只有25%。此外，日本受试者的每日脂肪摄入量显著增加（从9%增加到25%），胆固醇胆石症是过去50年中增长最快的消化系统疾病之一。本研究的目的是探讨代谢综合征的临床表现和胆囊结石的形成是否存在潜在的性别相关危险因素，方法：胆囊运动障碍促进胆囊结石的形成，胆囊收缩依赖于胆囊收缩素（CCK）及其受体（CCK-IR）。我们建立了CCK-1 R基因敲除（-/-）小鼠。研究了富含脂肪和蛋白质的饮食OA-2对体重、高脂血症以及污泥和胆结石形成频率的影响，并在野生型和CCK-IR（-/-）雄性和雌性小鼠之间进行了比较。与标准饮食（CRF-I）（5.6%脂肪和22.6%蛋白质）相比，OA-2饮食含有略高的蛋白质和脂肪（7.9%脂肪和27.6%蛋白质），但它们的总能量相似。断奶后，在所有动物中提供CRF-I直至3月龄。当年龄匹配的CCK-IR（-/-）和野生型雄性和雌性小鼠在3月龄时达到成熟时，开始给予OA-2饮食。其余动物继续给予CRF-I。在6月龄和12月龄时通过断头台处死小鼠，并收集血液以测量甘油三酯和胆固醇的血浆水平。胆囊被切除并归类为正常（胆囊透明），混浊（淤渣形成）和/或含有胆结石形成。只要提供CRF-I，在12月龄时，CCK-IR（-/-）雄性小鼠中污泥和/或胆结石形成的频率为3/8（35%），雌性小鼠中为4/9（45%），而在6月龄时没有观察到胆结石形成。另一方面，与CRF-I组相比，无论基因型如何，OA-2组雄性小鼠的体重和血浆脂质浓度均增加。在OA-2饮食下，在6月龄时观察到污泥和胆结石形成，不仅在CCK-IR（-/-）雄性小鼠中，而且在野生型雄性小鼠中。与此相反，雌性小鼠的参数并没有不同的两个dietes.Conclusion：雄性小鼠更容易蛋白质和脂肪丰富的饮食诱导的肥胖比雌性小鼠，高营养状态加速污泥和胆结石形成的雄性小鼠。
Background: The frequency of Japanese subjects over 20 years old with metabolic syndrome is 45.6% in men but just 16.7% in women. The reason why Japanese male subjects are more susceptible to metabolic syndrome than women is unknown. One possibility is the higher frequency of Japanese male subjects ( 40-70 years old) who had a drinking habit ( 67%), while that of female subjects was only 25%. In addition, daily fat intake was markedly increased in Japanese subjects ( from 9% to 25%), and cholesterol cholelithiasis is one of the most rapidly increasing digestive diseases during the past 50 years. The object of this study is to examine whether a potential sex-related risk factor exists in the manifestation of metabolic syndrome as well as gallstone formation.Methods: Gallbladder dysmotility accerelates gallstone formation and gallbladder contraction depends on cholecystokinin ( CCK) and its receptor ( CCK-IR). We developed CCK-IR gene knockout (-/-) mice. The effects of the fat- and protein-enriched diet OA-2 on body weight, hyperlipidemia, and frequencies of sludge and gallstone formation were examined, and compared between wild-type and CCK-IR(-/-) male and female mice. The OA-2 diet contains slightly higher protein and fat ( 7.9 % fat and 27.6 % protein) compared with a standard diet ( CRF-I) ( 5.6 % fat and 22.6 % protein), but their total energies are similar. After weaning, CRF-I was provided until 3 months of age in all animals. Administration of an OA-2 diet was started when age-matched CCK-IR(-/-) and wild-type male and female mice reached maturity, at 3 months of age. Administration of CRF-I was continued in the rest of the animals. Mice were sacrificed by guillotine at 6 and 12 months of age and the blood was collected to measure plasma levels of triglyceride and cholesterol. The gallbladder was removed and classified as normal ( clear gallbladder), clouded ( sludge formation), and/or containing gallstone formations.Results: As long as CRF-I was provided, the frequency of sludge and/or gallstone formation in CCK-IR(-/-) male mice was 3 of 8 ( 35%) and 4 of 9 ( 45%) in females at 12 months of age, whereas no gallstone formation was observed at 6 months of age. On the other hand, male mice fed OA-2increased their body weight and plasma lipid concentrations, compared with those fed CRF-I regardless of genotype. Under the OA-2 diet, sludge and gallstone formation was observed at 6 months of age, not only in CCK-IR(-/-) male mice but also in wild-type male mice. In contrast, parameters in female mice did not differ between the two diets.Conclusion: Male mice were more susceptible to protein- and fat-enriched diet-induced obesity than female mice, and hyper-nutritional status accelerated sludge and gallstone formation in male mice.