Department of Pharmacology, University of Oxford, UK.
J Nutr Biochem. 2012 Apr;23(4):332-40. doi: 10.1016/j.jnutbio.2010.12.009. Epub 2011 May 2.
Plasma total cysteine (tCys) is strongly and independently associated with obesity in large human cohorts, but whether the association is causal is unknown. Dietary cyst(e)ine increases weight gain in some rodent models. We investigated the body composition, metabolic rate and metabolic phenotype of mature C3H/HeH mice assigned to low-cystine (LC) or high-cystine (HC) diets for 12 weeks. Compared to LC mice, HC mice gained more weight (P=.004 for 12-week weight gain %), with increased fat mass and lean mass, and lowered O₂ consumption and CO₂ production by calorimetry. The HC mice had 30% increase in intestinal fat/body weight % (P=.003) and ∼twofold elevated hepatic triglycerides (P=.046), with increased expression of hepatic lipogenic factors, peroxisome proliferator-activated receptor-γ and sterol regulatory element binding protein-1. Gene expression of both basal and catecholamine-stimulated lipolytic enzymes, adipose triglyceride lipase and hormone-sensitive lipase was inhibited in HC mice adipose tissue. The HC mice also had elevated fasting glucose (7.0 vs. 4.5 mmol/L, P<.001) and a greater area under the curve (P<.001) in intraperitoneal glucose tolerance tests, with enhanced expression of the negative regulator of insulin signaling, protein tyrosine phosphatase-1B, in liver and adipose tissue. Overall, high cystine intake promotes adiposity and an adverse metabolic phenotype in mice, indicating that the positive association of plasma tCys with obesity in humans may be causal.
血浆总半胱氨酸（tCys）与大人群肥胖密切相关且具有独立性，但这种相关性是否具有因果关系尚不清楚。膳食半胱氨酸（Cys）增加了一些啮齿动物模型的体重增加。我们研究了分配给低半胱氨酸（LC）或高半胱氨酸（HC）饮食 12 周的成熟 C3H/HeH 小鼠的身体成分、代谢率和代谢表型。与 LC 小鼠相比，HC 小鼠体重增加更多（12 周体重增加的 P 值为 0.004%），脂肪量和瘦体量增加，通过量热法测量的 O₂消耗和 CO₂产生降低。HC 小鼠的肠道脂肪/体重比增加了 30%（P = 0.003），肝甘油三酯增加了约两倍（P = 0.046），肝脂肪生成因子、过氧化物酶体增殖物激活受体-γ和固醇调节元件结合蛋白-1的表达增加。HC 小鼠脂肪组织中基础和儿茶酚胺刺激的脂肪分解酶、脂肪甘油三酯脂肪酶和激素敏感脂肪酶的基因表达受到抑制。HC 小鼠的空腹血糖也升高（7.0 对 4.5 mmol/L，P<.001），腹腔内葡萄糖耐量试验的曲线下面积更大（P<.001），肝脏和脂肪组织中胰岛素信号负调节剂蛋白酪氨酸磷酸酶-1B 的表达增强。总的来说，高半胱氨酸摄入促进了肥胖和代谢不良表型在小鼠中的发生，表明血浆 tCys 与人类肥胖的正相关关系可能是因果关系。
