首份证据!小鼠试验发现:抑制它,可以不长胖
2018/05/10
在控制体重、减肥的问题上,最大的敌人往往是自己,因为身体会吸收所摄取食物的能量,并存储为脂肪。现在,科学家们找到了一种抑制脂肪累积的方法。他们以小鼠为模型发现,敲除脂肪组织中的一种关键酶NAMPT,可以完全阻止小鼠变胖或者超重。


这一最新研究发表在《Molecular Metabolism》期刊,来自于哥本哈根大学的科学家们发现,即便摄取高脂肪的食物(类似于汉堡包、披萨等高热量食物),缺乏NAMPT的突变小鼠也不会发胖!

文章一作、Novo Nordisk 基金会中心基础代谢研究学生 Karen Nørgaard Nielsen 希望,这一研究能够促成实现“解析肥胖机制”的最终目标,从而为代谢类疾病提供新的治疗线索。


DOI: https://doi.org/10.1016/j.molmet.2018.02.014

首个证据

NAMPT(烟酰胺磷酸核糖转移酶)是机体内一种关键酶,在细胞增殖、分化、凋亡、肿瘤、衰老和代谢中均有重要作用。之前已有研究表明,血液和胃部脂肪组织中表达的大量NAMPT与超重或者肥胖有关。

现在,这一最新研究首次证实,NAMPT是超重或者肥胖的必要因子。脂肪组织中缺乏NAMPT,可以完全阻止肥胖。

研究团队选用了两组动物:正常小鼠、脂肪组织缺乏NAMPT的突变小鼠。结果发现,当饮食正常时,两类小鼠的体重或者脂肪累积量没有差异。但是,摄取高脂肪食物后,正常小鼠会发胖,而突变小鼠体重却没有变化。而且,突变小鼠对血糖的控制能力也比正常小鼠好。

与传统认知相悖

“过去对于NAMPT的研究,多与其增强新陈代谢有关。例如,肝脏、肌肉可能受益于NAMPT活性的增加。” hary Gerhart-Hines副教授表示,“现在,我们发现NAMPT对于脂肪组织功能的发挥至关重要。遗憾的是,它是促进脂肪的存储。”

最后,他强调,直接抑制NAMPT或许并不可行,因为这会对身体其他组织带来巨大的风险。他希望,通过解析NAMPT与肥胖的关联,找到治疗肥胖、代谢类疾病的潜在靶标。

责编:悠然

参考资料:

Researchers defy biology: Mice remain slim on burger diet

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  • NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

    Objective The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+) biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) supports adipose plasticity and the pathological progression to obesity. Methods We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results Fat-specific Nampt knockout (FANKO) mice were completely resistant to high fat diet (HFD)-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions These findings indicate that adipose NAMPT plays an essential role in handling dietary lipid to modulate fat tissue plasticity, food intake, and systemic glucose homeostasis.

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