避免母乳產生毒素的內控奧秘(英漢對照)

牧童

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.


譯文來自丁香園：
http://www.dxy.cn/bbs/post/view?bid=116&id=9801820&sty=1&tpg=1&age=0

避免母乳產生毒素的內控奧秘


母乳由于其營養成分豐富，營養價值高以及容易取得而被認為是完美的食物。然而最新研究表明如果調控乳汁分泌的分子通道被破壞，母乳也會具有毒性。

以休斯醫學研究院研究員Ronald M. Evans為首的研究小組在2007年8月份的《基因與發育》雜志上報道,過氧化物酶體增殖劑激活受體-gamma蛋白（PPAR gamma）缺陷的母鼠可產生有毒性的乳汁。

Evans研究小組發現用血細胞以及排列于血管與淋巴管內部的細胞中產生PPAR gamma蛋白的基因缺失的母鼠乳汁喂養幼鼠時，可致幼鼠發生炎癥、生長發育遲緩以及脫毛。用PPAR gamma未發生遺傳變異的母乳喂養上述受累的幼鼠時，乳汁的毒性作用可得到逆轉。進一步研究顯示PPAR-gamma缺陷母鼠乳汁中含有可促使炎癥發生的氧化型脂肪酸和毒性物質。使用阿司匹林或其它的抗炎藥物也可逆轉上述乳汁的毒性作用。

PPARs是細胞核受體中被深入研究的一個家族，細胞核受體是負責感應激素和其它分子的蛋白。和其它蛋白一起調控基因的開放和關閉，與細胞內糖、脂肪和蛋白質的代謝密切相關。PPAR gamma是一種幫助調節體內糖和脂肪儲備的蛋白。

Evans說顯然這里存在著一個特定的機制用以保證乳汁的質量。 “我們沒有聽說過乳汁的毒性是因為存在著一個特定的系統來使之保持清潔。這是合理的，也是可以預料的。”

Evans認為PPAR gamma用來保證母乳質量這一作用可能是進化的基本特征。

PPAR gamma是用來改變體內的糖和脂肪的去向的，人類群體中調控PPAR gamma的遺傳程序設計存在著不同的變異。這一系統已經成為用抗炎藥物療法來處理像糖尿病這類情況的靶標。

wning

it is very informative.thank you so much for dilivering

sharplew

:tiaotiao: :sdsd: :sdsd: 無起步有

sharplew

好帖子，頂:hihi: :hihi: :hihi: :huahua: