Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice
Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice
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DOI：
10.2337/diabetes.53.12.3274
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Almind, K;Kahn, CR
饮食引起的肥胖是当前糖尿病流行的主要决定因素。我们使用低脂肪或高脂肪饮食的 C57B1/6 (B6)、129S6/SvEvTac (129) 和杂交 (B6 x 129)F2 小鼠探索了遗传学在这一现象中的作用。在 18 周的时间里，尽管食物摄入量较低，但 B6 和 F2 小鼠的体重增加了更多，胰岛素和瘦素水平更高，并且比 129 只小鼠表现出更严重的葡萄糖不耐受。相比之下，129 只小鼠的代谢率和饮食诱导的生热作用明显更高。全基因组扫描确定了几个数量性状位点，包括与 14 号染色体上的高胰岛素血症/胰岛素抵抗相关的数量性状位点，该区域与遗传诱导的胰岛素抵抗小鼠中所见的区域类似。微阵列分析表明，B6 和 129 小鼠之间 Wnt5a 和蛋白激酶 Cdelta (PKCdelta) 染色体区域的表达水平发生显着变化。因此，热量效率，即“节俭基因”，是小鼠饮食诱发肥胖的显性遗传决定因素，并且可能与 14 号染色体上的基因座相关，包括与脂肪发育和胰岛素敏感性相关的基因。
Diet-induced obesity is the primary determinant of the current, epidemic of diabetes. We have explored the role of genetics in this phenomenon, using C57B1/6 (B6), 129S6/SvEvTac (129), and intercross (B6 x 129)F2 mice on a low- or high-fat diet. Over an 18-week period, B6 and F2 mice gained more weight, had higher levels of insulin and leptin, and showed greater glucose intolerance than 129 mice, despite lower food intake. By contrast, metabolic rate and diet-induced thermogenesis were significantly higher in the 129 mice. Genome-wide scans identified several quantitative trait loci, including a quantitative trait locus that was linked with hyperinsulinemia/insulin resistance on chromosome 14 in a region similar to that seen in mice with genetically induced insulin resistance. Microarray analysis indicated significant changes in expression levels between B6 and 129 mice in the identified chromosomal area of Wnt5a and protein kinase Cdelta (PKCdelta). Thus, caloric efficiency, i.e., the "thrifty gene," is a dominant-acting genetic determinant of diet-induced obesity in mice and can be linked to a locus on chromosome 14, including genes linked to adipose development and insulin sensitivity.