避免母乳产生毒素的内控奥秘

kingburg

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Hidden Quality Control System Keeps Mothers from Producing Toxic Milk

Throughout human history, mother's milk has been regarded as the perfect food. Rich, nutritious and readily available, it is the drink of choice for tens of millions of human infants, not to mention all mammals from mice to whales.

But even mother's milk can turn toxic if the molecular pathways that govern its production are disrupted, according to a new study by Howard Hughes Medical Institute (HHMI) researchers at The Salk Institute for Biological Studies.

“It's one of those unexpected observations. It tells you the mother can transmit quite a bit more than nutrition through the milk.”
Ronald M. Evans

Writing in the August 2007 issue of the journal Genes & Development, a group led by HHMI investigator Ronald M. Evans reports that female mice that are deficient in the protein PPAR gamma produce toxic milk. The milk that had been nutritious instead causes inflammation, growth retardation and loss of hair in nursing mouse pups.

“We all think of milk as the ultimate food, the soul food for young animals,” said Evans. “The quality of that milk is also something that is genetically predetermined.”

In essence, the new finding reveals a genetic program for ensuring that mother's milk is the wonder food it is hailed to be: “We stumbled onto a hidden quality control system. Milk has to be a very clean product. It seems there is a whole process the body uses so that milk is scrubbed and doesn't have anything toxic in it.”

Evans said the finding was unanticipated, discovered when his group engineered mice to be deficient in PPAR gamma, a protein that helps regulate the body's sugar and fat stores. Mouse pups developed growth retardation and hair loss when they nursed on mothers who lacked the gene to produce PPAR gamma in blood cells and cells that line the interior of blood and lymph vessels.

“It's one of those unexpected observations,” Evans explained. “It tells you the mother can transmit quite a bit more than nutrition through the milk.”

Evans's group found they could reverse the toxic effects of the milk by letting the affected mouse pups nurse on a mother without the genetic variation in PPAR gamma.

Further studies showed that the mouse mothers with the PPAR-gamma deficiency produced milk with oxidized fatty acids, toxic substances that can prompt inflammation.

Evans and his colleagues showed that they could reverse the toxic effects of the milk by administering aspirin or other anti-inflammatory agents. “If you suppress the inflammation, the hair grows back,” said Evans.

PPARs are a widely studied family of nuclear receptors, proteins that are responsible for sensing hormones and other molecules. They work in concert with other proteins to switch genes on or off and are intimately connected to the cellular metabolism of carbohydrates, fats and proteins.

Although their discovery came as a surprise, Evans said it should have been obvious that there would be a mechanism in place to ensure the quality of milk.

“We should have realized there is something very special about it,” he said. “The reason we haven't heard about toxic milk is because there is a system that keeps it clean. It is logical and should have been anticipated.”

In Evans's view, PPAR gamma's role in ensuring the quality of mother's milk is likely to be a fundamental feature of evolution.

Lactating mothers, he noted, are not protected from inflammation, yet the milk they produce must be a pristine product: “Healthfulness in the body or products of the body is due to a (genetic) program, a process designed over the course of evolutionary history to maintain health.”

PPAR gamma's role in cleansing milk is “a very straightforward variation on how this system controls both lipid metabolism and inflammation. It's the secret of keeping them apart. That may be the reason the whole system exists,” Evans said.

In the human population, there are variants in the genetic program that governs PPAR gamma, which alters the fate of sugar and fat in the body. The system is already the target of anti-inflammatory drug therapy used to manage conditions such as diabetes.

Co-authors of the new Genes & Development article include Yihong Wan, Ling-Wa Chong and Chun-Li Zhang, all of The Salk Institute; and Alan Saghatelian and Benjamin F. Cravatt of The Scripps Research Institute.


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避免母乳产生毒素的内控奥秘


母乳由于其营养成分丰富，营养价值高以及容易取得而被认为是完美的食物。然而最新研究表明如果调控乳汁分泌的分子通道被破坏，母乳也会具有毒性。

以休斯医学研究院研究员Ronald M. Evans为首的研究小组在2007年8月份的《基因与发育》杂志上报道,过氧化物酶体增殖剂激活受体-gamma蛋白（PPAR gamma）缺陷的母鼠可产生有毒性的乳汁。

Evans研究小组发现用血细胞以及排列于血管与淋巴管内部的细胞中产生PPAR gamma蛋白的基因缺失的母鼠乳汁喂养幼鼠时，可致幼鼠发生炎症、生长发育迟缓以及脱毛。用PPAR gamma未发生遗传变异的母乳喂养上述受累的幼鼠时，乳汁的毒性作用可得到逆转。进一步研究显示PPAR-gamma缺陷母鼠乳汁中含有可促使炎症发生的氧化型脂肪酸和毒性物质。使用阿司匹林或其它的抗炎药物也可逆转上述乳汁的毒性作用。

PPARs是细胞核受体中被深入研究的一个家族，细胞核受体是负责感应激素和其它分子的蛋白。和其它蛋白一起调控基因的开放和关闭，与细胞内糖、脂肪和蛋白质的代谢密切相关。PPAR gamma是一种帮助调节体内糖和脂肪储备的蛋白。

Evans说显然这里存在着一个特定的机制用以保证乳汁的质量。 “我们没有听说过乳汁的毒性是因为存在着一个特定的系统来使之保持清洁。这是合理的，也是可以预料的。”

Evans认为PPAR gamma用来保证母乳质量这一作用可能是进化的基本特征。

PPAR gamma是用来改变体内的糖和脂肪的去向的，人类群体中调控PPAR gamma的遗传程序设计存在着不同的变异。这一系统已经成为用抗炎药物疗法来处理像糖尿病这类情况的靶标。