So the concentration of LDL cholesterol in a child is low.

是以，兒童體內的低密度脂蛋白膽固醇濃度較低。

The concentration of ApoB is low.

載脂蛋白 B 的濃度很低。

We don't see this very often because we're not used to checking these things in kids, but occasionally you'll even notice it as a parent if your kid gets sort of a comprehensive blood test that their total cholesterol might be 60 milligrams per deciliter with an LDL cholesterol of 30 milligrams per deciliter and an HDL cholesterol of 25 milligrams per I mean, they're very, very low levels of this.

我們不經常看到這種情況，因為我們不習慣給孩子檢查這些東西，但作為家長，如果你的孩子接受了某種全面的血液檢測，他們的總膽固醇可能是每分升 60 毫克，低密度脂蛋白膽固醇是每分升 30 毫克，高密度脂蛋白膽固醇是每分升 25 毫克，我的意思是，他們的膽固醇水準非常非常低。

Why does this change as we age?

為什麼隨著年齡的增長，情況會發生變化？

Why is it that aging seems to be associated with a monotonic increase in lipoproteins?

為什麼衰老似乎與脂蛋白的單調增加有關？

And this is absent something that we could even get to later if we have time, which is what happens during menopause for women, which is more abrupt.

如果有時間的話，我們甚至可以稍後再討論這個問題。

But just talk to me about ages, you know, 10 to 50.

但只要跟我談談年齡，你知道的，10 歲到 50 歲。

Why does everybody seem to go the wrong way?

為什麼每個人似乎都走錯了路？

Well, a lot of, of course, is the multitude of things we subject our bodies to.

當然，這其中有很多原因是我們的身體承受了許多東西。

If you want to encompass that with the environment or a lifestyle, you quote, unquote, whatever, and you can throw probably whatever you want into that category of things that might cause your body to, as ApoB goes up, it's almost all related to your liver is losing the ability to clear these particles out of plasma.

如果你想用環境或生活方式來概括這一點，你可以引用 "隨便 "這個詞，你可以把任何你想要的東西都歸入這一類，這些東西可能會導致你的身體載脂蛋白B升高，這幾乎都與你的肝臟失去從血漿中清除這些微粒的能力有關。

It's not like you're overproducing 10 tons of them.

又不是超量生產 10 噸。

It can happen, but that's rarely a contributor to the high ApoB levels.

這種情況有可能發生，但很少會導致載脂蛋白 B 水準過高。

So scientifically, we have to zero in on what regulates clearance of these particles.

是以，在科學上，我們必須找出是什麼在調節這些微粒的清除。

And the simplest thing is to say, well, the only way these ApoB particles get cleared is our liver produces something called an LDL receptor, which migrates to the surface of the liver cell that interacts with the blood flow, the plasma, and these LDL receptors are engineers to recognize any ApoB peptide that floats by it.

最簡單的說法是，這些載脂蛋白B顆粒被清除的唯一途徑是我們的肝臟產生一種叫做低密度脂蛋白受體的東西，它會遷移到與血流、血漿相互作用的肝細胞表面，這些低密度脂蛋白受體是工程師，能夠識別漂浮在它周圍的任何載脂蛋白B肽。

So if an LDL particle containing ApoB floats by an LDL receptor, it will get grabbed, and then it gets internalized into the LDL receptor, and it gets catabolized, and then the liver can take whatever cholesterol, triglycerides, fatty acids, blah, blah, blah, is in that molecule and use it for other purposes or somehow get rid of it in the biliary system if the liver doesn't need it.

是以，如果含有載脂蛋白 B 的低密度脂蛋白顆粒漂浮在低密度脂蛋白受體旁邊，它就會被抓住，然後被內化到低密度脂蛋白受體中，並被分解，然後肝臟就可以吸收分子中的膽固醇、甘油三酯、脂肪酸等等等等，並將其用於其他用途，或者在肝臟不需要的情況下，通過某種方式在膽道系統中將其排出體外。

So it's going to come down to what are these factors that I called, hey, environmental lifestyle that affects what we call LDL receptor expression, and it's a lot of things.

是以，這要歸結為我所說的影響我們所謂的低密度脂蛋白受體表達的環境生活方式的因素是什麼，這涉及到很多方面。

One of the things you mentioned before, insulin resistance would affect that, numerous components of the diet express, are you regulating LDL receptors or not, how much cholesterol your liver is being told it needs to put in the next VLDL particle, or more importantly, the HDL particle going out.

你之前提到的其中一件事，胰島素抵抗會影響這一點，飲食中的許多成分會影響這一點，你是否調節了低密度脂蛋白受體，你的肝臟被告知需要將多少膽固醇放入下一個 VLDL 顆粒中，或者更重要的是，高密度脂蛋白顆粒會被排出體外。

So lipid balance in the liver is regulated by a bunch of things called nuclear transcription factors, and they actually sense, hey, the liver needs some lipids or the liver's got too much lipids and we've got to get rid of it.

是以，肝臟中的脂質平衡是由一堆叫做核轉錄因子的東西調節的，它們實際上是在感知：嘿，肝臟需要一些脂質，或者肝臟的脂質太多了，我們得把它排出去。

Those nuclear transcription factors migrate into the nucleus and the nucleolus of our cells, and they bind to specific parts of the DNA and tell our genes, produce this protein, produce that protein, this enzyme, that enzyme, this receptor, that receptor, that can go out and help restore sterile homeostasis to this human body.

這些核轉錄因子遷移到細胞核和核仁中，與 DNA 的特定部分結合，告訴我們的基因，產生這種蛋白質、產生那種蛋白質、這種酶、那種酶、這種受體、那種受體，從而幫助人體恢復無菌平衡。

So probably every adversarial thing you've been told in your life not to do, gain weight, don't eat this, don't eat that, are all affecting these nuclear transcription factors that are going to regulate clearance of these ApoB particles, and it's a long list of things that can probably do that.

是以，在你的生活中，可能每件你被告知不要做的不利事情，比如體重增加、不要吃這個、不要吃那個，都會影響到這些核轉錄因子，而這些核轉錄因子會調節載脂蛋白B顆粒的清除，這是個很長的清單，可能有很多事情都會影響到載脂蛋白B顆粒的清除。

It is interesting that, on average, more of the things that we do that are, quote-unquote, less healthy, whether it be gain weight, eat a certain way, tends to result in decreased hepatic clearance.

有趣的是，平均而言，我們所做的更多不太健康的事情，無論是增加體重還是以某種方式進食，都會導致肝臟清除率下降。

So on that topic, one of the questions you and I get asked all the time is, look, hey, doc, I kind of buy your thesis that ApoB is bad, I buy your thesis that mine is too high, and I buy your thesis that I should probably lower it.

是以，關於這個話題，你和我經常被問到的一個問題是，醫生，我相信你的理論，載脂蛋白B不好，我相信你的理論，我的載脂蛋白B太高，我相信你的理論，我也許應該降低它。

I'd really like to start with my diet before I turn to pharmacology.

我真的想先從飲食入手，然後再進行藥物治療。

You know, typically, there's two things I tell patients here.

我通常會告訴病人兩件事。

The first is, I think your two best levers nutritionally to reduce ApoB are lowering triglycerides and lowering saturated fat intake.

首先，我認為降低載脂蛋白 B 的兩個最佳營養槓桿是降低甘油三酯和飽和脂肪的攝入量。

Now, of course, this assumes that you have high enough triglycerides that lowering them further will indeed lower ApoB, and it, of course, assumes you're eating a high enough amount of saturated fat that reducing it significantly will lower ApoB.

當然，這要假定您的甘油三酯足夠高，進一步降低甘油三酯確實會降低載脂蛋白B，當然，這也要假定您攝入的飽和脂肪足夠多，大幅減少飽和脂肪會降低載脂蛋白B。

So let's assume for a moment that those things are true.

所以，讓我們暫時假設這些事情都是真的。

We're talking to a patient, Tom, whose ApoB is 100 milligrams per deciliter.

我們正在和一位病人湯姆談話，他的載脂蛋白B是每分升100毫克。

You know, you and I have just kind of, I don't want to say read him the riot act, but we've given him the education that says, look, you'd be a heck of a lot better off if you were at 60 milligrams per deciliter.

你知道，你和我只是一種，我不想說讀他的暴動法案，但我們已經給了他的教育說，你看，你會是一個赫克很多更好，如果你在每分升60毫克。

His triglycerides are sitting at about 162 milligrams per deciliter, and when we query his diet, we realize it's pretty high in saturated fat.

他的甘油三酯約為每分升 162 毫克，當我們查詢他的飲食時，發現飽和脂肪含量很高。

He's probably getting, you know, call it, I don't know, 40 or 50 percent of his calories from fat, and he's probably getting, you know, 50, 60 grams per day of saturated fat alone.

他可能攝入的，你知道，我不知道，40%或 50%的熱量來自脂肪，他可能每天攝入 50 或 60 克飽和脂肪。

So in other words, he seems like a really ideal candidate if he's willing to switch more of his fat calories to monounsaturated and polyunsaturated or even just reduce fat altogether, and he's willing to take the dietary steps to reduce total calories and maybe even carbohydrates specifically to kind of bring down his triglycerides.

是以，換句話說，如果他願意將更多的脂肪熱量轉換為單不飽和和多不飽和熱量，甚至只是完全減少脂肪，並且願意採取飲食措施減少總熱量，甚至可能專門減少碳水化合物，以降低甘油三酯，那麼他似乎就是一個非常理想的人選。

So without getting into how he's going to do that, can you explain why lowering triglycerides and lowering saturated fat intake, those two things, could bring this guy from 100 down to 60?

所以，在不涉及他如何做到這一點的情況下，你能解釋一下為什麼降低甘油三酯和飽和脂肪的攝入量，這兩點可以讓這個人從100降到60嗎？

Sure.

當然。

The saturated fat is a little easier to explain.

飽和脂肪比較容易解釋。

We have plenty of studies that show excess saturated fat, those genes that are regulating lipid or those nuclear transcription factors that are regulating lipid balance in the liver, and the liver is the master controller of lipid homeostasis in the body.

我們有大量的研究表明，過量的飽和脂肪、那些調節脂質的基因或那些調節肝臟中脂質平衡的核轉錄因子，而肝臟是體內脂質平衡的主要控制者。

It works hand-in-hand with the intestine, but the liver is sort of the brains of the operation.

肝臟與腸道協同工作，但肝臟是整個運作的大腦。

So in many, many people, exposure to saturated fat, the nuclear transcription factors realize, oh my God, fatty liver, fatty acid toxicity is going to occur to this liver.

是以，很多人在接觸飽和脂肪後，核轉錄因子就會意識到，天哪，脂肪肝、脂肪酸毒性會對肝臟造成影響。

We have to take our defensive mechanisms on that.

我們必須採取相應的防禦機制。

So what they first thing they do is say, my God, we don't want more lipids being pulled into the liver by these LDL receptors.

是以，他們做的第一件事就是說，天哪，我們不希望這些低密度脂蛋白受體把更多的血脂拉入肝臟。

So the nuclear transcription factors go into your DNA and say, stop making these LDL receptors.

是以，核轉錄因子會進入你的 DNA，然後說，停止製造這些低密度脂蛋白受體。

Stop sending out the signal that will be translated into an LDL receptor.

停止發出將轉化為低密度脂蛋白受體的信號。

So of course, if you eat saturated fat and your liver stops expressing LDL receptors, your ApoB is going to go through the roof.

當然，如果你攝入飽和脂肪，肝臟停止表達低密度脂蛋白受體，你的載脂蛋白B就會上升。

What is the ApoB particle carrying? And above the threshold concentration, it's going in the artery wall.

載脂蛋白B顆粒攜帶著什麼？ 超過閾值濃度，它就會進入動脈壁。

Typically, if that person does follow your advice and restricts the saturated fat, they will go back to some more increase in their LDL receptor expression.

通常情況下，如果這個人聽從您的建議，限制飽和脂肪的攝入，他們的低密度脂蛋白受體表達會再次增加。

All right.

好吧

The saturated fat in some people, too, also turn on the enzymes that induce cholesterol synthesis.

有些人體內的飽和脂肪也會開啟誘導膽固醇合成的酶。

So now if the liver starts overproducing cholesterol, then the lipid pool is out of whack.

是以，如果肝臟開始過度分泌膽固醇，那麼脂質庫就會出現問題。

The same nuclear transcription factors go in and say, stop making the LDL receptors.

同樣的核轉錄因子會說，停止製造低密度脂蛋白受體。

We don't want to pull in more cholesterol into this liver that's oversynthesizing cholesterol.

我們不想讓膽固醇合成過多的肝臟吸收更多的膽固醇。

So that's it.

就是這樣。

It's another whole story, as you know, Peter, why we don't necessarily tell people you have to restrict cholesterol in your diet.

彼得，你也知道，為什麼我們不一定要告訴人們在飲食中限制膽固醇的攝入量，這又是另一回事了。

We're talking about saturated fat here.

這裡說的是飽和脂肪。

And the absorption of sterols in your gut has nothing to do with the absorption of fatty acids in your gut.

而腸道對固醇的吸收與腸道對脂肪酸的吸收毫無關係。

Totally different mechanisms that pull them in.

吸引他們的機制完全不同。