Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice
Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice
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DOI：
10.1152/ajpendo.00259.2003
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发表时间：
2003-12-01
影响因子：
5.1
通讯作者：
Kraemer, FB
中科院分区：
文献类型：
--
作者：
Harada, K;Shen, WJ;Kraemer, FB
为了阐明脂肪酶敏感性脂肪酶（HSL）在饮食诱导的肥胖中的作用，将HSL缺陷型（HSL-/-）和野生型小鼠饲喂正常食物或高脂饮食。HSL-/-小鼠对饮食诱导的肥胖有抗性，显示出更高的核心体温。HSL-/-小鼠的体重和三酰甘油含量在白色脂肪组织（WAT）中降低，但在棕色脂肪组织（BAT）和肝脏中增加。HSL-/-小鼠进食状态下的血清胰岛素水平和脂肪组织中肿瘤坏死因子-α mRNA水平较高，而WAT中脂肪细胞补体相关蛋白30 kDa（ACRP 30）/脂联素和瘦素的血清水平以及ACRP 30/脂联素、瘦素、瘦素和脂蛋白酶的mRNA水平均低于对照组。脂肪形成相关转录因子的表达（过氧化物酶体增殖物激活受体-γ，CAAT/增强子结合蛋白-α）和脂肪生成（碳水化合物反应元件结合蛋白、脂肪细胞决定和分化依赖因子1/固醇调节元件结合蛋白-1c），以及脂肪分化标志物（脂肪细胞脂质结合蛋白、围脂蛋白、脂蛋白脂酶）、脂肪生成酶（甘油-3-磷酸酰基转移酶，酰基-CoA：二酰基甘油酰基转移酶-1和-2、脂肪酸合成酶、ATP柠檬酸裂解酶）和胰岛素信号传导蛋白（胰岛素受体，胰岛素受体底物-1，GLUT 4）在HSL-/-小鼠的WAT中被抑制，但在BAT中未被抑制。相反，与胆固醇代谢（固醇调节元件结合蛋白-2，3-羟基-3-甲基戊二酰辅酶A还原酶，酰基辅酶A：胆固醇酰基转移酶-1）和产热（解偶联蛋白-2）相关的基因的表达在HSL-/-小鼠的WAT和BAT中均上调。我们的研究结果表明，受损的脂肪分解HSL缺乏影响脂质代谢，通过改变脂肪分化和脂肪源性激素水平。
To elucidate the role of hormone-sensitive lipase (HSL) in diet-induced obesity, HSL-deficient (HSL-/-) and wild-type mice were fed normal chow or high-fat diets. HSL-/- mice were resistant to diet-induced obesity showing higher core body temperatures. Weight and triacylglycerol contents were decreased in white adipose tissue (WAT) but increased in both brown adipose tissue (BAT) and liver of HSL-/- mice. Serum insulin levels in the fed state and tumor necrosis factor-alpha mRNA levels in adipose tissues were higher, whereas serum levels of adipocyte complement-related protein of 30 kDa (ACRP30)/adiponectin and leptin, as well as mRNA levels of ACRP30/adiponectin, leptin, resistin, and adipsin in WAT, were lower in HSL-/- mice than in controls. Expression of transcription factors associated with adipogenesis (peroxisome proliferator-activated receptor-gamma, CAAT/enhancer-binding protein-alpha) and lipogenesis (carbohydrate response element-binding protein, adipocyte determination- and differentiation-dependent factor1/sterol regulatory element-binding protein-1c), as well as of adipose differentiation markers (adipocyte lipid-binding protein, perilipin, lipoprotein lipase), lipogenic enzymes (glycerol-3-phosphate acyltransferase, acyl-CoA: diacylglycerol acyltransferase-1 and -2, fatty acid synthase, ATP citrate lyase) and insulin signaling proteins (insulin receptor, insulin receptor substrate-1, GLUT4), was suppressed in WAT but not in BAT of HSL-/- mice. In contrast, expression of genes associated with cholesterol metabolism (sterol-regulatory element-binding protein-2,3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA: cholesterol acyltransferase-1) and thermogenesis (uncoupling protein-2) was upregulated in both WAT and BAT of HSL-/- mice. Our results suggest that impaired lipolysis in HSL deficiency affects lipid metabolism through alterations of adipose differentiation and adipose-derived hormone levels.