β-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency
β-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency
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DOI：
10.1038/oby.2008.337
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发表时间：
2008-09-01
期刊：
影响因子：
6.9
通讯作者：
Fromenty, Bernard
中科院分区：
文献类型：
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作者：
Begriche, Karima;Massart, Julie;Fromenty, Bernard
β-氨基异丁酸（BAIBA），一种胸腺嘧啶的分解代谢物，增加了瑞士（瘦）小鼠肝脏中的脂肪酸氧化（FAO），并减少了标准食物喂养的体脂肪量的增加。我们在不同的小鼠模型中确定了BAIBA是否可以预防肥胖和相关的代谢紊乱。为此，在完全缺乏瘦素的小鼠（ob/ob）中给予BAIBA（1100或500 mg/kg/天）4个月。在喂食高热量（HC）饮食的野生型（+/+）小鼠和瘦素部分缺乏（ob/+）小鼠中，也给予BAIBA（100 mg/kg/天）4个月。BAIBA没有限制肥胖和肥胖小鼠的肝脏脂肪变性，但减少了肝脏细胞溶解和炎症。在喂食HC饮食的ob/+小鼠中，BAIBA完全预防或限制了体脂增加、脂肪变性和坏死性炎症、葡萄糖耐受不良和高脂血症。血浆β-羟基丁酸增加，而肉毒碱棕榈酰转移酶-1的表达增加，在肝脏和白色脂肪组织。乙酰辅酶A羧化酶磷酸化程度更高，肝脏中诱导的从头脂肪生成较少。BAIBA对ob/+小鼠的这些有利作用与血浆瘦素水平的恢复有关。在+/+小鼠中，BAIBA提供的身体肥胖减少不太明显。最后，BAIBA显著刺激分离的ob/+脂肪细胞分泌瘦素，但不刺激+/+细胞。因此，BAIBA可以通过瘦素依赖性的FAO刺激来限制组织中甘油三酯的增加。由于部分瘦素缺乏症在一般人群中并不罕见，补充BAIBA可能有助于预防低瘦素分泌者的饮食诱导的肥胖和相关代谢紊乱。
beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (1100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.