#405 ‒ 第88期AMA：代谢性肝脏健康：如何评估风险、早期发现功能障碍，以及预防或逆转肝病

嘿，大家好。

Hey, everyone.

欢迎收听《The Drive》播客的AMA抢先预览集。

Welcome to a sneak peek ask me anything or AMA episode of the drive podcast.

我是你们的主持人，阿提亚。

I'm your host, Attia.

在这集短节目的最后，我会告诉大家如何完整收听AMA集，以及我们为会员准备的其他一大堆福利。

At the end of this short episode, I'll explain how you can access the AMA episodes in full along with a ton of other membership benefits we've created.

或者你现在就可以去peterattiamd.com/subscribe了解更多。

Or you can learn more now by going to peterattiamd.com forward slash subscribe.

话不多说，下面就是今天AMA集的抢先预览。

Without further delay, here's today's sneak peek of the Ask Me Anything episode.

欢迎收听第88集AMA问答节目。

Welcome to Ask Me Anything AMA episode 88.

今天我们要聊的是肝脏，特别是它在代谢健康中的作用。

Today, we are talking about the liver, and specifically its role in metabolic health.

这个话题存在一个奇怪的错位。

This is a topic that suffers from a strange mismatch.

一方面，肝脏是人体中代谢最重要的器官之一。

On the one hand, the liver is one of the most metabolically important organs in the body.

它是处理葡萄糖、脂肪和胆固醇的核心枢纽。

It is the mastermind sitting at the center of how we handle glucose, fat, and cholesterol.

另一方面，公众对肝脏的讨论大多集中在排毒、清洁和补品上，而真正重要的问题却没人问。

On the other, most of the public conversation about the liver is about detoxes, cleanses, and supplements, while the questions that actually matter go unasked.

我们将聚焦肝脏的一个主要功能，即它如何成为全身代谢的核心，并探讨如何判断你的肝脏是否承受压力，为什么这很重要，以及一旦需要行动，什么措施才能真正起作用。

We're going to focus on one of the liver's main functions, how it serves as the centerpiece of the whole body metabolism, and walk through how to tell whether yours is under stress, why that matters, and what actually moves the needle once you need to act.

具体来说，我们将讨论为什么肝脏被称为代谢功能障碍的“金丝雀”，从代谢压力到纤维化的四个进展阶段，以及哪些阶段是可逆的，为什么正常的肝酶可能具有误导性，我们实际上用什么来检测终末期风险，一旦发现风险或疾病，哪些干预措施有效，以及诚实评估是否有任何肝脏补品值得服用。

Specifically, we're going to cover why the liver is the so called canary in the coal mine for metabolic dysfunction, the four stages of progression from metabolic stress to fibrosis, and which stages are reversible, why normal liver enzymes can be misleading and what we actually use to detect end stage risk, what interventions work once risk or disease is identified, plus an honest look at whether any liver supplements are worth taking.

如果你是订阅者，想观看本期播客的完整视频，可以在节目说明页面上找到。

If you're a subscriber and you want to watch the full video of this podcast, you can find it on the show notes page.

如果你不是订阅者，可以在我们的YouTube页面观看视频预览。

And if you're not a subscriber, you can watch a sneak peek of the video on our YouTube page.

话不多说，欢迎来到AMA第88期。

Without further delay, welcome to AMA episode 88.

彼得，

Peter,

欢迎来到又一期AMA。

welcome to another AMA.

你最近怎么样？

How are doing?

挺好的。

Pretty good.

谢谢。

Thanks.

太好了。

Awesome.

那么今天，我们整期节目都围绕一个话题，就是肝脏和代谢健康。

So today, we are doing the whole episode around one topic, which is the liver and metabolic health.

你之前把肝脏形容为代谢功能障碍的“金丝雀”，就是煤矿里的金丝雀那种预警信号。

In the past, you've described the liver as the quote, unquote canary in the coal mine for metabolic dysfunction.

所以我觉得咱们可以先聊聊你这话是什么意思，以及为什么你觉得肝脏这么重要。

So I think it'd be helpful to start with kind of talking about what you mean by that and why you think the liver is so important.

嗯，肝脏可以说是全身代谢的中心，负责处理所有宏量营养素，包括葡萄糖、脂肪、蛋白质，还有胆固醇。

Well, the liver sits sort of at the center of systemic metabolism for every macronutrient, glucose, fat, protein, as well as cholesterol.

对了，别忘了还有乙醇，也就是酒精。

By the way, let's not forget ethanol or alcohol there as well.

它也是身体里最早感知压力、并且对压力做出反应的地方之一，不管是哪个系统出了问题。

It's also one of the very first places to both promote and respond to stress from anywhere in the system.

如果血液里的甘油三酯偏高，肝脏就会参与进来。

If circulating triglycerides are high, the liver gets involved.

如果血糖调节出了问题，肝脏也脱不了干系。

If glucose regulation is deteriorating, the liver's involved.

如果ApoB或低密度脂蛋白胆固醇升高，那些颗粒就是肝脏制造的。

If ApoB or LDL cholesterol is climbing, the liver made those particles.

反过来也是一样的。

The flip side is equally true.

如果我们看到肝脏处于压力之下，就知道这些代谢系统也处于压力之下。

If we look at the liver and see that it's under stress, we know that these metabolic systems are also under stress.

全身代谢健康和肝脏状况就像两面镜子，互相映照。

It's a two way mirror between systemic metabolic health and what's happening in the liver.

这也是为什么我不把肝病看作一个孤立的器官问题。

That's also why I think about liver disease less about a standalone organ problem.

肝脏功能紊乱更像是全身代谢紊乱的一种平行表现。

Dysfunction of the liver is more of a parallel expression of systemic metabolic dysfunction.

肝病患者的主要死因不是肝衰竭，而是心血管疾病，因为代谢压力下的肝脏会过度产生含ApoB的颗粒，并加剧胰岛素抵抗，从而推动全身动脉粥样硬化。

The leading cause of death in people with liver disease isn't liver failure, it's cardiovascular disease, because a liver under metabolic stress is overproducing ApoB containing particles and amplifying the insulin resistance that drives atherosclerosis throughout the body.

所以这既是肝脏问题，更是代谢问题。

That's why this is a metabolic episode as much as a liver one.

我想我们也应该一开始就说明这一点。

I guess we should also name it upfront.

说到脂肪肝，这是一种据估计影响全球超过38%成年人的疾病，这真的很难相信。

When we're talking about fatty liver disease, we're talking about a disorder that is estimated to affect more than thirty eight percent of the world's adult population, which is hard to believe.

这不是那种发生在某个你永远不会遇到的倒霉人身上的事。

This isn't something that happens to some unfortunate person that you'll never meet.

在发达国家，几乎任何不注意的人都会得这个病。

It will happen to nearly anyone in the developed world who isn't paying some attention.

我觉得我们一开始应该聊聊肝脏是做什么的。

And I think it's worth kind of early on talking about what the liver does.

对吧？

Right?

所以我觉得很多人想到肝脏时，通常想到的是解酒。

So I think for a lot of people, when they think of the liver, they usually think about processing alcohol.

在我们深入讨论代谢疾病之前，你能更详细地讲讲肝脏在身体里到底起什么作用吗？

So before we get too much into metabolic disease, can you frame in a little more detail what the liver is doing in the body?

当然。

Sure.

你说得对。

And you're right.

大家确实都只想到酒精，但这其实有点低估了肝脏的作用。

The alcohol framing dominates, and and that's a bit of an undersell.

就像我们之前的嘉宾Julia Watercero说的，肝脏有超过300种功能，这真的挺惊人的。

As our past guest, Julia Watercero says, the liver has over 300 functions, which is sort of staggering.

当然，我们今天不会讨论那么多，但我觉得可以把这些功能归纳成四大类，这样比较好理解。

Obviously, we're not going to talk about many of those today, but I find it useful to conceptualize all of those as fitting into four main categories.

第一类是解毒。

So the first is detoxification.

肝脏分解酒精，就像它分解几乎任何进入体内的毒素一样，不管是来自食物、饮料、药物还是吸入的东西。

The liver breaks down alcohol, just as it would break down virtually any toxin that makes its way into the body from food, drink, pharmaceuticals, inhalation.

任何进入血液的毒素，肝脏都在清除过程中起核心作用。

Any toxin that reaches the blood, the liver plays a central role in clearing it.

第二，肝脏是免疫器官。

Second, it is an immune organ.

血液从肠道出来的第一站就是肝脏。

The first place blood from the gut goes is to the liver.

所有从肠道出来的血液都会通过门静脉系统回到肝脏。

All, blood from the gut winds its way back into the portal system to the liver.

所以肝脏是应对摄入毒素或肠道细菌渗漏的第一道防线之一。

So it's one of the first responders to ingested toxins or bacterial leakage from the gut.

第三是蛋白质的处理和分泌。

Third is protein processing and secretion.

我们血液中许多最常见的蛋白质都是在肝脏合成的。

The liver is the site of synthesis for many of the most common proteins in our blood.

像白蛋白这样普遍存在的，还有凝血因子、血小板生成刺激因子、ApoB，以及像IGF-1这样的肽类激素，这些都很重要。

Something as ubiquitous as albumin and as vital as clotting and platelet stimulating factors, ApoB, peptide hormones like IGF-one.

第四类是我们今天要重点讨论的，那就是能量代谢。

The fourth category is where we're going to spend most of our time today, and that is on energy metabolism.

肝脏在循环脂肪和胆固醇的吸收与合成中起着核心作用，而且它还是维持血糖平衡最重要的器官之一，甚至可以说就是最重要的器官。

The liver plays a central role in the uptake and synthesis of circulating fats and cholesterol, and is one of the most important organs, if not the most important organ, for the balancing act of maintaining blood sugar.

你可以把它看作是人体的代谢总部，所以当它受损时，伤害不仅仅局限于这个器官本身。

It's you you could think of it as the metabolic headquarters of the body, which is why when it's harmed, the damage is not just confined to the organ itself.

你刚才提到了肝脏和血糖。

You mentioned there about the liver and blood sugar.

你能更详细地讲讲肝脏和血糖控制之间的关系吗？

Can you walk us through more the liver's relationship with controlling blood sugar?

好的。

Yeah.

听起来简单，但调节血糖所需的精确度非常惊人，我每次都觉得不可思议。

It sounds simple, but the precision required, to regulate blood sugar is extraordinary, and it never ceases to amaze me.

这是我最喜欢向病人解释的事情之一。

It's one of my favorite things to explain to a patient.

饭后，血糖会升高。

After a meal, glucose rises.

胰腺会释放胰岛素，胰岛素告诉肝脏吸收葡萄糖并将其储存为糖原。

The pancreas releases insulin and insulin tells the liver to absorb glucose and store it as glycogen.

现在，当你禁食一段时间后，血糖下降，胰岛素水平降低，肝脏就会反过来运作。

Now, when you've been fasting for some period of time and glucose dips, insulin falls and then the liver does the opposite.

它会把糖原重新分解，释放葡萄糖到血液中。

It breaks glycogen back down and releases glucose into the circulation.

当血糖非常低的时候，肝脏甚至可以自己制造葡萄糖。

When glucose runs really low, it can actually just manufacture glucose on its own.

如果你超过一天不进食，肝脏就会变成一个制造葡萄糖的器官。

If you're going more than a day without eating, the liver turns into a glucose making organ.

如果糖分太多，无法全部储存为糖原，肝脏就会把它转化为甘油三酯，打包进载脂蛋白，然后运出去。

If there's too much sugar to store as glycogen, the liver converts it into triglycerides, packages it into apolipoproteins, and ships them out.

所以，我想让大家明白的是，这个过程的规模有多大。

So what I want people to appreciate though is the scale of this.

大家想想，你去医院抽血，通常是空腹抽血，对吧？

So everybody, you know, think about you go to the doctor, you get a blood draw, and it's, you know, it's a fasting blood draw, right?

然后你拿到一个数值。

And you get back a number.

比如说，你拿到的那个数字是90毫克每分升。

And so let's say that number you get back says 90 milligrams per deciliter.

那就是你那天早上到实验室时的血糖水平。

That was your blood glucose that morning when you showed up at the lab.

如果是这样的话，你当时整个血液里总共只有大约4.5克葡萄糖。

If that's the case, your entire bloodstream in that moment contained only about four and a half grams of glucose.

这大概就是一茶匙的量，不是一汤匙，就是一茶匙。

That's roughly a teaspoon, not a tablespoon, just a teaspoon.

但是，一顿饭，尤其是我吃的那种饭，可能含有好几倍这个量，轻松就能达到90克葡萄糖，对吧？

Yet a single meal, especially if it's a meal that I'm eating, may contain many times that, easily 90 grams of glucose, right?

所以，一顿饭就是那个量的20倍。

So, 20 times that amount in one meal.

尽管如此，健康人的血糖水平很少会超出基线一茶匙的量，对吧？

Yet despite that, a healthy person rarely moves more than a teaspoon above baseline, right?

实际上，我在想我戴连续血糖监测仪的时候，有没有见过血糖水平超过160毫克每分升的情况。

In fact, I'm trying to think of all the times I wore a continuous glucose monitor if I ever saw a blood glucose lever that would have been north of about 160 milligrams per deciliter.

二型糖尿病患者在空腹时也很少超过一茶匙半。

Someone with type two diabetes would rarely go above a teaspoon and a half at fasting.

即使我们几个小时不吃东西，血糖仍然保持在这个范围内。

When we can go hours without eating, our glucose still stays in that range.

事实上，如果你几天不吃东西，血糖可能只会降到大约50毫克每分升。

In fact, if you go days without eating, it might only dip to say 50 milligrams per deciliter.

这是一个了不起的体内平衡成就，而这种以如此精细的量释放葡萄糖的储备能力，正是早期功能障碍很容易被忽视的原因，这一点我们肯定会在后面讨论。

This is a monumental homeostatic achievement, and that reserve capacity to titrate out glucose in such fine amounts is exactly why early dysfunction is very easy to miss, which is something we'll, I'm sure, talk about.

对。

Yeah.

那我们就深入聊聊代谢疾病以及它如何影响肝脏吧。

And so let's dive into more metabolic disease and how that affects the liver.

在讨论这个问题时，你通常有没有一个框架，用来向患者解释？

And so when looking at that, is there a framework that you typically use, typically talk through with patients in explaining it?

是的。

Yeah.

我觉得最有用的框架是把代谢性肝病分成四个阶段来看。

I think the most useful framing is to consider metabolic liver disease moving through four stages.

第一阶段，肝脏开始出现代谢压力。

In the first stage, the liver becomes metabolically stressed.

第二阶段，为了应对这种压力，肝脏开始储存多余的能量，也就是脂肪，这种情况叫做脂肪变性。

Then the second stage, in response to that, it starts storing excess, excess energy that is, as fat, and that's a condition known as steatosis.

第三阶段就是脂肪性肝炎。

Then the third stage is steatohepatitis.

说白了就是肝脏里堆积了太多脂肪，导致肝脏发炎，然后肝脏开始损伤自己。

That is just a fancy word for excess fat being stored in the liver, tips the liver into inflammation, and then the liver begins to injure itself.

第四阶段就是肝脏对损伤的反应，开始形成疤痕组织。

Then the fourth stage is the response to that injury where it starts to lay down scar tissue.

这个大家可能听说过，叫肝纤维化。

That's a term that people have probably heard called fibrosis in the liver.

前三个阶段基本上都是可逆的。

Those first three stages are largely reversible.

纤维化就有点棘手了。

It's fibrosis that is a little trickier.

它在生物学上是可以不同程度逆转的，尤其是在非常早期发现的时候。

It is biologically reversible to varying degrees, especially if caught on the very, very early side of things.

但一旦疤痕积累到肝脏结构被破坏的程度，那就变得不可逆了。

But once the scarring accumulates into such that the liver's architecture is disrupted, that's the point that becomes irreversible.

纤维化的存在是预测我们通常关心的结果的关键，尤其是心血管疾病、癌症，甚至肝脏相关的死亡率。

Now, the presence of fibrosis is what predicts the outcomes that we typically care about, especially cardiovascular disease, cancer, and even liver specific mortality.

在我们进行这个讨论的过程中，我会不断提醒大家我们处于这个四阶段框架中的哪个位置。

As we kind of go through this exercise, I'll keep pointing back to where we are on that four part scheme.

你之前说过，长期热量过剩是代谢功能障碍的主要驱动因素。

You've previously said that chronic calorie surplus is a primary driver of metabolic dysfunction.

你能带我们梳理一下从热量过剩到最终肝损伤的整个事件链吗？

Can you walk us through the chain of the events from caloric surplus to ultimately at the end, liver damage?

是的。

Yeah.

这开始相对简单。

It starts relatively simply.

如果你持续摄入的热量超过消耗，身体就必须把多余的能量存起来，肝脏会通过从头脂肪生成的过程，把其中大部分转化为甘油三酯。

If you consume more calories than you expend consistently, the body has to put that excess energy somewhere, and the liver converts much of it into triglycerides through a process of de novo lipogenesis.

肝脏把这些甘油三酯包装成含有ApoB的颗粒，也就是VLDL和LDL，然后运送到脂肪组织进行长期储存。

It packages them into these ApoB containing particles, namely VLDLs and LDLs, and ships them to adipose tissue for long term storage.

再说一遍，这是一种正常健康的生理反应。

Again, that is a normal healthy physiologic response.

如果我们没有这种能力，我们今天就不会在这里。

If we didn't have that capacity, we wouldn't be here today.

你和我也不会在这里交谈。

You and I wouldn't be talking together.

我们的物种早就灭绝了，因为我们必须能够在能量充足时储存能量，在能量稀缺时从中提取。

Our species would have gone extinct because we had to be able to store energy when energy was abundant, and we had to be able to draw from that when energy was scarce.

到目前为止，这都是正常的。

So far, this is normal.

显然，你也看到了，这迟早会变得不正常。

It's obviously, as you can see, it's going to become abnormal at some point.

把脂肪细胞想象成一个仓库。

Think of a fat cell as a warehouse.

一开始，它们会接收每一批货物。

For a while, they will accept every shipment.

但随着它们逐渐被填满，它们对胰岛素的反应就不再正常了，而胰岛素是这个过程里最关键的一种激素。

But as they become progressively overfilled, they stop responding normally to insulin, which is kind of the most important hormone that's involved in this process.

这个过程的一个分子标志是二酰甘油（也叫DAG）这种脂质中间体的积累，它会干扰胰岛素信号。

One of the molecular hallmarks of that process is the accumulation of a lipid intermediate called diacylglycerol or DAG or DAG, which interrupts insulin signaling.

一旦发生这种情况，仓库就开始出问题了。

Once that happens, the warehouse starts malfunctioning.

这些脂肪细胞不再只是储存脂肪，反而开始把脂肪酸释放回血液里，这恰恰是你不想看到的，除非你马上就要用掉它们。

Instead of simply storing fat, those particular fat cells or adipocytes begin releasing fatty acids back into the bloodstream, exactly what you don't want unless you're about to use them immediately.

问题在于，血液里已经有太多能量了。

The problem is there's already too much energy in circulation.

你最不希望看到的就是更多的甘油三酯被释放回血液里。

The last place you want more triglycerides is being released back into the bloodstream.

所以现在肝脏不仅要处理从饮食中摄入的多余热量，还要处理那些有问题的脂肪细胞释放回血液中的多余脂肪。

So now the liver has to deal not only with the excess calories coming in from the diet, but also the excess fat coming back into the circulation from those defective fat cells.

血液中的游离脂肪酸会怎么样？

What happens to the free fatty acids in the blood?

肝脏会吸收这些脂肪酸以及我们饮食中的脂肪，因为能量平衡是它的主要工作之一。

The liver picks up those fatty acids as well as the fats from our diet, because that's one of the primary jobs, is energy balance.

但最终，同样的过程也会在这里发生。

But eventually the same process develops here.

于是脂质中间产物开始积累，胰岛素信号传导受损，肝脏就变得胰岛素抵抗了。

So lipid intermediates begin to accumulate, insulin signaling becomes impaired, and the liver becomes insulin resistant.

大家可能还记得我们之前和Ralph DiFranco做的那期播客，那是我过去一两年最喜欢的播客之一，因为它就像一堂关于各种胰岛素抵抗的大师课。

Now, people may recall back to the podcast that we did with Ralph DiFranco on this, and it was a it's one of my favorite podcasts of the past year or two because it's just a masterclass in all of the different types of insulin resistance.

肌肉、脂肪细胞、胰腺和肝脏的胰岛素抵抗，它们看起来都有点不同。

Insulin resistance in the muscle versus the fat cell versus the pancreas versus the liver, they all look a little bit different.

这个我现在不细讲，但如果有人想好好复习一下，我们会在播客里放链接。

I'm not going to get into that now, but if anybody wants to sort of get really brushed up on that, that's where we'll go, we'll link to that in the podcast.

但接下来这部分非常重要。

But here's the part that's really important.

胰岛素通常告诉肝脏做两件事：停止向血液中释放葡萄糖，以及停止制造新的脂肪细胞。

Insulin normally tells the liver to do two things, stop releasing glucose into the bloodstream and stop making new fat cells.

为什么？

Why?

因为胰岛素高，说明你刚吃过饭。

Because if insulin is high, you've just been fed.

既然吃过饭了，就不需要往血液里放葡萄糖，也不需要让你变胖。

If you're fed, you don't need to be putting glucose into the bloodstream or making you fat.

但随着胰岛素抵抗的发展，第一个信号先失效，第二个后失效。

But as insulin resistance develops, the first signal fails before the second.

肝脏在血糖已经很高的情况下继续释放葡萄糖，而胰腺则通过分泌更多胰岛素来应对，这仍然会推动脂肪的产生。

The liver continues releasing glucose even when blood sugar is already high, while the pancreas responds by making more insulin, which still drives fat production.

这叫做选择性肝脏胰岛素抵抗，是代谢疾病的一个典型特征。

That's called selective hepatic insulin resistance, and it's one of the defining features of metabolic disease.

一开始，肝脏会把那些甘油三酯打包进含有ApoB的颗粒里，也就是我们常说的低密度脂蛋白和极低密度脂蛋白，所以血脂异常总是伴随这种情况出现。

At first, the liver exports those triglycerides in these ApoB containing particles, and again, that just means LDLs and VLDLs, which is why dyslipidemia always accompanies this.

最终，生产的速度超过了输出的速度。

Eventually, production outpaces exports.

脂肪开始在肝脏里堆积，这时候我们就进入了这个线性发展过程的第二阶段。

Fat accumulates inside the liver, and now we've reached stage two of our little linear progression.

这就是脂肪肝了。

This is now steatosis.

那这种代谢功能障碍会导致哪些肝脏疾病，是你比较担心的？

What are the liver diseases that you're concerned about as a result of that metabolic dysfunction?

其实这个病的名字最近改了，更新是为了反映病因，不再把“脂肪”放在名字里，因为脂肪只是热量过剩的最终结果，而过剩的热量通常不是脂肪本身。

Well, the name changed recently, updated to reference the cause of the disease and move away from the fat in the name because fat is at the is basically the end result of caloric excess, but that excess isn't usually fat itself.

多余的热量往往来自各种食物。

Excess calories are often in the form of anything.

可能是碳水化合物、葡萄糖、果糖。

It could be carbohydrates, glucose, fructose.

基本上，我们之前把这种病叫做NAFLD，也就是非酒精性脂肪肝。

Basically, earlier we called this disease NAFLD, non alcoholic fatty liver disease.

如果它发展到炎症损伤阶段，就叫NASH，也就是非酒精性脂肪性肝炎。

Then if it progressed to the inflammation damage stage, it was NASH, which just stood for non alcoholic steatohepatitis.

顺便说一下，这两个名字里的“非酒精性”是为了说明这种病主要是由能量过剩引起的，而不是酒精本身造成的损伤，因为酒精也可能导致酒精性脂肪肝和酒精性脂肪性肝炎。

By the way, the NA in both of those non alcoholic is just so that we try to understand that this was driven more through excess energy, but not through the damage specifically of alcohol, because you could also get alcoholic fatty liver disease and alcoholic steatohepatitis.

好的。

Okay.

现在这些病被称为MASLD，M-A-S-L-D，是MASLD，不是那个电视剧。

Now these things are called MASLD, M A S L D, and MASLD, not the TV show.

这个缩写代表什么呢？

What does that stand for?

它代表代谢功能障碍相关的脂肪性肝病和脂肪性肝炎。

That stands for metabolic dysfunction associated steatotic liver disease and steatohepatitis.

其实还是同一种病，只是换了新名字。

Basically, it's the same disease, just new names.

我先提前道个歉。

I'm going to apologize in advance.

我偶尔还是会用NAFLD和NASH这两个旧名字，而不是MASLD和NASH。

I will occasionally still refer to these as NAFLD and NASH as opposed to MASLD and NASH.

再次提前说声抱歉，但请理解，这只是为了更准确地反映疾病过程而采用的新术语。

Again, apologies in advance for that, but please understand it's just new nomenclature to try to more accurately reflect the process of the disease.

说到这个，一旦脂肪堆积起来，是不是肝脏就开始受到实际损伤了？

And on that, so once fat is built up, is that the point at which the liver starts to suffer actual damage?

脂肪肝是一个巨大的警示信号。

Well, steatosis is a giant warning sign.

虽然还不是肝损伤，但你已经走在通往肝损伤的路上了。

It's not liver damage yet though, but you're sort of now on the path to liver damage.

你可以把它想象成肝脏把多余的能量库存塞进经理办公室，因为货架已经满了。

So think of it as the liver stuffing excess energy inventory into the manager's office because the shelves are full.

很明显出了问题，但在包装车间里，还没有东西坏掉。

Something is clearly wrong, but at the packaging facility, nothing is breaking yet.

如果这个比喻有帮助的话，可能没有。

If that analogy helps, it might not.

MASLD 的诊断标准是脂肪肝伴随另一种心血管代谢风险因素，比如高血压、糖化血红蛋白定义的糖尿病前期，或者甚至就是二型糖尿病本身、血脂异常、BMI 升高或肥胖。

MASLD is diagnosed when that steatosis is accompanied by another cardiometabolic risk factor, such as hypertension, prediabetes defined by hemoglobin A1C, or even just type two diabetes itself, dyslipidemia, elevated BMI or obesity.

再说一次，这些只是粗略的替代指标，但你明白我的意思，对吧？

Again, these are just sort of poor man's proxies, but you get the point, right?

也就是说，我们要找的是肝脏脂肪加上某种其他代谢功能障碍。

Which is liver fat accompanied by some other metabolic dysfunction is what we're looking for.

所以这就是我们的第二阶段，既有代谢压力，又有肝脏脂肪。

So that's our second stage, both metabolic stress as well as fat in the liver.

真正的损伤始于脂肪负担引发炎症。

The real damage begins when that fat burden triggers inflammation.

肝细胞超负荷后，实际上开始死亡。

Hepatocytes loaded past their limit actually start to die.

肝细胞就是构成肝脏的细胞。

Hepatocytes are just the cells that make up the liver.

这些细胞死亡后，会吸引免疫细胞过来，它们释放炎症信号，扩散到周围的细胞。

Their death recruits immune cells, which release inflammatory signals that spread to neighboring cells.

正是这种炎症，通过另一条独立的通路，开始破坏胰岛素信号传导。

It's that inflammation that starts to disable insulin signaling through a second separate pathway.

现在，胰岛素抵抗从两个方向同时袭来。

The resistance is now coming from two directions at once.

随着胰岛素抵抗加重，周围的细胞也积累更多脂肪，然后也死掉，接着就形成一波扩散，每个细胞的死亡都会引发下一个细胞的死亡。

With even more insulin resistance, the neighboring cells now accumulate more fat and die too, and then you get a spreading wave where each cell death drives the next.

你看，这就变成了一个正反馈的放大循环。

As you can see, this becomes a feed forward kind of amplified loop.

从脂肪堆积到活跃炎症的这个转变，就是从第二阶段进入第三阶段，也就是我们所说的MASH。

That transition, fat accumulating to active inflammation, is the move from stage two to stage three, what we call MASH.

肝脏对细胞死亡的反应，和其他组织一样。

The liver responds to dying cells the way any tissue does.

它会形成疤痕组织。

It lays down scar tissue.

这叫做纤维化。

That's called fibrosis.

这是我们考虑肝脏代谢疾病的最后阶段。

It's our final stage of thinking about metabolic disease in the liver.

随着纤维化的累积，肝脏会走向肝硬化。

As fibrosis accumulates, the liver moves towards cirrhosis.

那是终末期的疤痕，大量有功能的组织被替代，肝脏甚至无法再正常工作。

That's the end stage scarring where so much functioning tissue has been replaced that the liver can't even do its job anymore.

你得回想我之前讲的那些功能，比如制造蛋白质、凝血因子、解毒，这些都会逐渐丧失。

You have to think back to all those other things I talked about, making proteins and clotting factors and doing detoxification, all that stuff starts to go out the window.

这也是癌症风险开始急剧上升的阶段。

This is also where cancer risk starts to climb dramatically.

纤维化才是真正长期临床风险所在。

Fibrosis is where the really durable, clinical risk lives.

说到代谢功能障碍时，我们经常也会听到内脏脂肪。

And when talking about metabolic dysfunction, we often hear visceral fat as well.

那么关于肝脏里的内脏脂肪，我们了解多少呢？

So what do we know about visceral fat in the liver?

内脏脂肪会特别影响肝脏吗？

Does visceral fat affect the liver specifically?

是的。

Yes.

它是影响肝脏风险最重要的因素之一。

It's one of the most significant modifiers of liver risk.

不是所有脂肪在代谢上都是一样的。

Not all fat is meaning or metabolically equal.

储存在器官周围的脂肪，即使在基础状态下也更容易释放脂肪酸。

Fat stored around your organs is actually more prone to releasing fatty acids even at baseline.

但更大的因素绝对是位置。

But the bigger factor is definitely location.

所以内脏脂肪，也就是腹部器官周围的脂肪，会直接流入门静脉，而门静脉是通往肝脏的两条血液供应之一。

So visceral fat, fat around the abdominal organs drains directly into the portal vein, which is one of the two blood supplies that goes to the liver.

门静脉负责引流胃肠道，所以所有的肠道和消化产生的代谢物都通过它。

It's the one that drains the GI tract, so all of the gut and all of the metabolites that come from digestion.

皮下脂肪释放的脂肪酸先扩散到全身循环中，所以对肝脏来说，浓度远没有那么集中，不是直接冲击。

Subcutaneous fat releases fatty acids that diffuse through the entire circulation first, so it's just far less concentrated in terms of a shot directly into the liver.

内脏脂肪则完全绕过了这些。

Visceral fat bypasses, all of that.

所以这就像有人隔着房子对你喊，和直接对着你耳朵喊的区别。

So it's the difference between someone yelling at you from across the house versus shouting directly into your ear.

信号一样，但因为来源不同，强度就高得多。

Same signal, but just much higher intensity because of where it's coming from.

数据也证实了这一点。

The data bear this out.

在一个队列研究中，通过CT扫描估算的内脏脂肪面积，能独立于BMI和肝酶预测脂肪肝。

In one cohort, visceral fat area, which could be estimated by CT scans, predicted steatosis independent of BMI and liver enzymes.

内脏脂肪面积超过200平方厘米的患者，肝脏脂肪变性的风险比低于100平方厘米的人高出7.5倍。

Patients with greater than two hundred centimeters squared of visceral fat had a seven and a half fold greater increase of liver steatosis when compared to people below 100 centimeters squared.

如果看NHANES数据库，在确诊为MASLD的人群中，内脏脂肪最高四分位数的全因死亡率几乎是最低四分位数的3.5倍。

If you looked at the NHANES database among people with diagnosed MASLD, the all cause mortality ratio in the top quartile of visceral adiposity was nearly three and a half times that in the lowest quartile.

内脏脂肪能预测肝脏病变，而且对于已经患有肝病的人来说，内脏脂肪预示着死亡风险显著升高。

Visceral fat predicts liver pathology, And in the people who already have liver disease, visceral fat predicts a dramatically higher risk of death.

过去在讨论代谢健康时，你经常提到抗阻训练的重要性。

And in the past, when talking about metabolic health, you've often talked about the importance of resistance training.

那么，关于抗阻训练如何与肝脏在代谢功能障碍中的作用相互影响，我们了解多少呢？

So what do we know about how does resistance training interact with the role of the liver in metabolic dysfunction?

其实，比肝脏更重要的是，骨骼肌是身体中主要的葡萄糖消耗器官。

Well, even more so than the liver, skeletal muscle is a major glucose sink in the body.

事实上，它绝对是身体中最大的葡萄糖消耗器官。

In fact, it is hands down the largest sink of glucose in the body.

它能把血液中的糖分抽出来，以糖原的形式储存起来。

It pulls blood sugar out of circulation and stores it as glycogen.

大致来说，你储存葡萄糖的总能力中，大约四分之三在肌肉里，四分之一在肝脏里。

So roughly speaking, about three quarters of your total capacity to store glucose is in your muscle and about a quarter of it's in your liver.

同样是以糖原的形式储存。

That's again storing it as glycogen.

肌肉少意味着什么？

Less muscle means what?

那就意味着缓冲葡萄糖的能力下降，所以更多的负担落在了肝脏上。

Therefore means less capacity to buffer glucose, so more of that burden lands on your liver.

这就是为什么你会看到一些BMI正常但肌肉量很低的人患上代谢性肝病。

It's why you see metabolic liver disease in people that actually have normal BMI, but are very low in muscle mass.

这种情况的术语叫肌少性肥胖，也就是人们常说的“瘦胖子”。

Sarcopenic obesity is the technical term for that or what people call skinny fat.

多项纵向队列研究都指出了同样的事实。

Multiple longitudinal cohorts point the same thing out.

肌肉量越多，不仅新发MASLD的病例更少，而且病情缓解率也更高。

More muscle predicts both fewer new cases of MASLD and higher rates of resolution.

最引人注目的数据来自韩国一项为期七年的大型队列研究。

The single most striking figure comes from a large seven year Korean cohort.

在研究期间肌肉增长最多的人，其MASLD缓解率是肌肉增长最少者的四倍多。

People who gained the most muscle over the study resolved their MASLD at more than four times the rate of those who gained the least muscle.

我们会在节目笔记中附上所有这些内容。

We'll include all of this in the show notes.

所以无论是预防还是逆转，方向都非常明确，这就是为什么如果你想解决代谢功能障碍，力量训练几乎是必不可少的。

So whether it's prevention or reversal, the direction here is pretty unambiguous, which is why resistance training is kind of a non negotiable if you're trying to address metabolic dysfunction.

我们是否知道果糖是否比葡萄糖更有害？

Do we know anything about if fructose may be more harmful than glucose?

这个问题非常有趣，而且很容易让人纠结。

This is a very interesting question and one that it's very easy to get wrapped around the axle on this one.

最干净的人体实验——我只想关注人体实验，因为如果我们想讨论所有动物实验，尼克，我们可能一整天都聊不完这个问题。

The cleanest human experiment and I only want to focus on the human experiments because you could we could spend the entire day on this question, Nick, if we wanted to talk about all of the animal stuff.

但最干净的人体实验是一项随机试验，涉及94名健康男性，他们在七周内保持体重稳定，饮用了适量含果糖、蔗糖（即果糖和葡萄糖各占一半的混合物）或葡萄糖的甜味饮料。

But the cleanest human experiment is a randomized trial in 94 healthy men who drank moderate amounts of fructose, which is again, just the pure sweet enantiomer, sucrose, which is the fiftyfifty mix of fructose and glucose, or glucose sweetened beverages for seven weeks at weight stability.

做这类研究时，保持受试者体重稳定非常重要，因为如果不这样做，所有结果都会被混淆。

It's very important when you do these studies that you have to keep the subject's weight stable because if you don't, it confounds everything.

在这项研究中，果糖和蔗糖大约使肝脏的基础脂肪生成机制翻倍，也就是所谓的“从头脂肪生成”通路。

In this study, fructose and sucrose roughly doubled the liver's baseline fat making machinery, this so called de novo lipogenesis pathway.

“从头”就是新的意思，“脂肪生成”就是制造脂肪，而葡萄糖却没有这种效果。

De novo just means new and lipogenesis means fat creating, while glucose did not.

至少在这项研究中，果糖在人体肝脏中的作用与葡萄糖不同。

At least in this study, fructose can behave differently from glucose in the human liver.

这一点最明显地体现在从头脂肪生成的测量结果上。

Where that shows up most cleanly is in these measurements of de novo lipogenesis.

但在更硬性的指标，即实际的脂肪肝上，控制饮食的研究表明，主要驱动因素是热量过剩，而不是果糖本身。

But on the harder outcome, actual steatosis, controlled feeding studies show the dominant driver is excess calories and not fructose itself.

如果用等热量的其他碳水化合物替代果糖，肝脏脂肪几乎不变。

If you swap fructose isocalorically for other carbohydrates, liver fat barely moves.

从卡路里对卡路里的角度看，果糖特有的真实信号体现在脂肪生成上，这是一个中间指标，而不是最终结果。

Calorie for calorie, the honest fructose specific signal is on lipogenesis, which is an intermediate measure, but not the final outcome.

果糖之所以名声在外，是因为它进入人体的方式。

Where fructose earns its reputation is in the form that it arrives in.

比如汽水里的液态糖，或者其他含高果糖玉米糖浆的饮料，热量密度很高，喝了不容易有饱腹感，而且特别容易喝多。

Liquid sugar in soda, for example, or other high fructose corn syrup laden beverages, which are very calorie dense, don't make you feel full, and are trivially easy to consume.

队列研究确实把含糖饮料和更高的非酒精性脂肪肝病或代谢相关脂肪性肝病风险联系起来。

The cohort data do link sugar sweetened beverages to higher NAFLD risk or MASLD risk.

实际建议依然成立：减少含糖饮料，对于胰岛素抵抗或肝病患者来说，绝对是回报率很高的饮食调整之一。

The practical advice holds, cutting sugar sweetened beverages is absolutely one of the higher yield dietary moves for someone with insulin resistance or liver disease.

但真正的主要原因在于，这样做最终会减少热量摄入。

But it's really the chief reason for that is that it's going to have its downstream effect on less calorie reduction.

所以，如果有人有脂肪肝，我一定会建议他们：完全不要喝含热量的饮料，尤其是含碳水化合物的饮料，特别是含果糖的饮料。

So one of the things I absolutely would counsel somebody on who has fatty liver disease is don't drink calories at all, and especially don't drink carbohydrate calories and especially don't drink fructose containing calories.

这句话里包含了很多专业要点。

A lot of specialties there in that statement.

听起来非常重要。

Sounds like it was super important.

好的。

Alright.

那么现在回到我们之前聊过的话题，就是人们一提到肝脏，就会想到酒精。

So going now to what we talked about earlier on, which is when people think about the liver, they think about alcohol.

那么我们应该如何看待酒精和肝脏的关系呢？

So how should we think about alcohol here as it relates to the liver?

对。

Yeah.

酒精的问题其实很明确。

Alcohol is a pretty clean story.

你记得刚才说过，我们之所以要在前面加上“非酒精性”之类的词，就是为了区分它。

You'll recall a second ago, said that the reason we have to put the NA, nonalcoholic or, you know, whatever, in front of those to differentiate it.

酒精本身就能导致脂肪肝。

It can cause fatty liver on its own.

酒精相关性肝病，其实比我们想象的要常见得多。

Alcohol associated liver disease, which by the way, is more common than we give it credit for.

大家很容易只关注非酒精性代谢性肝病。

It's very easy to just focus on the nonalcoholic metabolic versions.

但如果你看看需要肝移植的人，我不记得最新的数据，但上次我看的时候，我很惊讶有多少人是因为酒精而不是非酒精因素导致的。

But if you actually look at the people requiring liver transplants, I don't remember the latest numbers, but the last time I looked, I was very surprised at how many I think more of those came from alcohol consumption than than nonalcoholic consumption.

再说一次，我可能记错了，但我记得当时挺惊讶的。

Again, I I could be off on that, but I just remember being sort of surprised.

不过，酒精是通过不同的机制起作用的，不像热量过剩那样，但结果几乎是一样的。

Now that said, it works through a different mechanism than caloric excess, but it turns out the outcome is almost the same.

你会经历脂肪变性、胰岛素抵抗、纤维化，最终到肝硬化这些阶段。

You pass through these categories of steatosis, insulin resistance, fibrosis, ultimately cirrhosis.

机制不同，所以如果和代谢功能障碍一起出现，那危害就很大了，这种情况很常见。

Different mechanism, which is why it's very harmful if you combine it with metabolic dysfunction, as is often the case.

所以当热量过剩和酒精同时存在时，你基本上会受到双重协同的攻击。

So now you're getting basically a two pronged synergistic attack when you have calorie excess and alcohol co occurring.

代谢功能障碍和酒精摄入的组合最近有了自己的命名，说实话，我觉得我们有点超前了，叫做代谢和酒精相关肝病，简称METHOLD。

The combination of metabolic dysfunction and alcohol consumption recently earned its own designation, which frankly, I think we're getting a little ahead of ourselves, which is metabolic and alcohol associated liver disease or METHOLD.

我再也不会说那个词了。

I'm not going to say that ever again.

NHANES数据库里有一项很有说服力的队列研究，研究对象是已有心血管代谢风险因素的患者。

There's a very telling cohort study from the NHANES database in patients with existing cardiometabolic risk factors.

如果你已经有风险因素，单纯脂肪肝并不会增加全因死亡率，但脂肪肝加上他们所说的适量饮酒——我可能会称之为适量偏多——全因死亡率的风险比是1.4，癌症死亡率是2.35，还有一个惊人的15。

If you already had a risk factor, steatosis alone wasn't associated with increased all cause mortality, but steatosis plus what they described as moderate, and I might call moderate plus alcohol consumption, produced hazard ratios of 1.4 for all cause mortality, 2.35 for cancer mortality, and a whopping fifteen.

请再核实一下那个数字。

Please check that number again.

是的，肝脏相关死亡率是15倍，相比没有脂肪肝的人。

Yes, 15x for liver specific mortality versus people with no steatotic liver disease.

把这些转换成实际的相对风险，就是任何原因导致的死亡风险增加了40%。

To put those into actual relative risks, that's a cause of death from anything is up forty percent.

癌症死亡风险增加了135%。

Death from cancer is up one hundred and thirty five percent.

而肝脏相关疾病的死亡风险增加了1400%。

And from liver specific disease, death is up fourteen hundred percent.

再说一遍，我分享这个的目的不是让你永远别喝酒，而是想说明，当你把酒精加到肝病上，情况会变得非常糟糕。

Again, the purpose of me sharing this is not to tell you never to have another drink, it's to explain that when you add alcohol to liver disease, it gets really bad.

现在，如果我们看看饮酒的模式，可能还是有一些值得借鉴的地方。

Now, if we look at the pattern of drinking, there might be some, again, something to glean here.

乙醛是酒精对肝脏造成伤害的主要因素。

Acetaldehyde is the primary driver of alcohol's harm on the liver.

当你每小时超过大约一杯酒时，乙醛积累的速度会更快。

It accumulates faster the more you exceed about one drink per hour.

因此，从机制上讲，我经常被问到这个问题，但我觉得我们可以说，一晚上喝七杯酒可能比连续七个晚上每晚喝一杯酒对你的伤害更大。

Therefore, mechanistically, I get asked this question all the time, but I think what we could say is seven drinks in one evening is probably worse for you than one drink per night, seven consecutive nights.

再说一次，我还没看到相关数据，但当你理解了作用机制，我觉得这是合理的。

Again, I haven't seen the data for that, but when you understand the mechanism of action, think that makes sense.

但基本上，我认为重点是，直接比较暴饮和每日饮酒对人类代谢疾病影响的数据并不存在。

But that's basically, I think the point here is that human data directly comparing binge versus daily drinking don't exist for the metabolic disease.

我怀疑我们不会有相关的随机对照试验，但这正是关于酒精和代谢性肝病的要点。

I suspect we're not going to have an RCT for that, but that's kind of the point on alcohol and metabolic liver disease.

接着NHANES研究的话题，我们知不知道他们实际喝了多少酒？

And to follow-up on the NHANES study, do we know how much alcohol they were actually drinking?

对。

Yeah.

再说，所有数据都是自我报告的，所以有可能他们喝的就是这么多。

Again, everything is self reported, so it's possible that this is what they were drinking.

也有可能这个数字稍微低估了。

It's also possible this is a slight underestimate.

我记得男性每天大概喝四十到六十克，女性的话需要少一些。

I believe the men were drinking something to the tune of forty to sixty grams a day, and the women would have needed to be a bit less than that.

我们会在节目笔记里放上具体数字，但这意味着这些人自我报告每天至少喝三杯，可能四杯。

We'll put the exact numbers in the show notes page, but that means that these are people that are self reporting three at least three drinks a day, maybe four drinks a day.

因为，再说，60克乙醇对于正常大小的杯子来说，可能还不到三杯，如果你自己倒的话，可能更少。

Because, again, 60 grams of ethanol is technically for normal sized drinks or potentially less if you're drinking, you know, if you're pouring it yourself.

尼克，我还想补充一点，很多人能喝这么多，而且完全正常生活。

The point I would also add to that, Nick, is there are lots of people who can drink that amount, and they're totally functional.

所以我不希望人们把这个解读为只针对那些酗酒成性的人，因为很多人每天喝三杯酒，显然也没有明显的副作用。

So I'd I'd I don't want the interpretation to be this is only for people, you know, who are rampant alcoholics because there lots of people can be drinking three drinks a day and obviously have, you know, no obvious side effects of that.

那么，我们继续往下看，除了生活方式因素之外。

And so moving beyond just lifestyle factors.

在检查肝脏时，有没有哪些人从一开始就处于更高的风险，无论是由于遗传、激素还是其他原因？

So when looking at the liver, are there any people who are at greater risk at the baseline, whether that's from genetics, hormones, or something else?

是的。

Yep.

我会把这些分为两类：一类是遗传因素，另一类是激素因素，后者会随时间波动。

I would put these into two buckets, the inherited genetic piece and then obviously the hormonal piece, which can fluctuate over time.

在遗传方面，这里最重要的单基因变异是一种叫做PNPLA3的东西。

So on the inherited side, the most important single gene variant here is something called PNPLA3.

携带这种特定变异两个拷贝的人，肝脏脂肪堆积的风险或可能性大约是两倍。

And people who carry two copies of a particular variant here tend to have about two X the risk of or the likelihood of accumulating liver fat.

即使考虑了标准的代谢风险因素，这也会带来炎症和纤维化风险的升高。

Then with that comes the elevated risk of inflammation and fibrosis, even after accounting for standard metabolic risk factors.

还有一些基因变异看起来是有保护作用的，特别是HSD17B13基因的一种功能缺失变异，这种变异与较低的肝酶水平和纤维化风险相关。

There are also variants that appear protective, especially a loss of function variant in a gene called HSD17B13, which is associated with lower liver enzymes and fibrosis risk.

而且它可能部分抵消PNPLA3带来的风险。

And it may actually partially offset the PNPLA3 associated risk.

还有其他一些基因变异。

There are other variants as well.

再说一遍，为了完整起见，我们会在节目笔记里列出它们，但我觉得更重要的点是，确实存在遗传易感性，甚至还有一些保护性因素。

Again, we'll kind of list them in the show notes for completeness, but I think the larger point here is that there is an absolute genetic predisposition and even some protection that we see.

我想任何临床医生都能证实这一点。

I think any clinician can attest to this.

对吧？

Right?

你总会遇到这样的病人，不管什么原因，两个人做完全相同的事情，但肝脏健康状况却完全不同。

You've got that patient who, for whatever reason, two people doing the exact same things and they have completely different liver health.

这也是为什么祖先背景会在人群风险中体现出来，不过我们得小心，不要夸大这一点。

It's also why ancestry can show up in population level risk, though, you know, we have to be careful not to overstate it.

所以PMPLA3风险变异在西班牙裔人群中更为常见。

So the PMPLA three risk variant is much more common in people with Hispanic ancestry.

这就是为什么在人群层面上，我们知道西班牙裔对MASLD和MASH更为敏感，也更容易患病。

So that's why at the population level, we know that Hispanics are much more sensitive to and therefore susceptible to MASLD and MASH.

而在非洲裔人群中，情况恰恰相反。

And it's actually the exact opposite in people of African ancestry.

这很可能解释了我们在临床上看到的现象。

So that likely contributes to what we see clinically.

但再说一次，这并不意味着在个体层面上总是如此。

But again, that doesn't mean at the individual level, that's always the case.

所以我不希望听这个节目的黑人朋友觉得，太好了。

So I don't want someone who's listening to this who's black to think, great.

我肯定不会得MASLD，那我就可以随便吃了。

I can't get MASLD, you know, away I go.

我也不希望西班牙裔的朋友听了之后说，哦，那太好了。

And I don't want someone who's Hispanic to listen to this and say, oh, well, great.

这是我的命运。

This is my destiny.

但再说一次，这只是易感性，你知道，它不是命运。

It's just again, it's a predisposition, but it's it's, you know, it's not destiny.

所以，我的意思是，现在还有一些身体成分的差异，标准化验和BMI这些东西常常会漏掉。

So, I mean, there are also now body composition differences that standard labs and BMI stuff can always miss.

比如，许多有亚洲血统的人在正常或较低的BMI下就会出现代谢风险，部分原因还是因为，在那些本来就不容易积累太多皮下脂肪的人群中，在给定的体重下，内脏脂肪可能更高。

For example, many people who are of Asian ancestry develop metabolic risk at lower and normal BMIs in part, again, because visceral adiposity can be higher at a given body weight in a group of people who otherwise don't genetically accumulate much subcutaneous fat.

所以，这就是为什么我认为体重和BMI，虽然在人群水平上是有用的工具，但在个体水平上却毫无意义。

So again, this is why I think body weight and BMI, while at the population level are useful tools, at the individual level offer nothing.

我无法告诉你我某个病人的BMI是多少，但我几乎能告诉你他们每个人的全身脂肪、内脏脂肪以及其他更细致的测量数据。

I wouldn't be able to tell you the BMI of one of my patients, but I can tell you virtually every one of their total body fat, visceral fat, and other measurements that are more nuanced.

那才是真正重要的。

That's what really matters.

另一个主要的基线调节因素是更年期。

The other major baseline modifier menopause.