00:00
Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia. And today I want to chat about something that I listened to on another podcast actually a couple of weeks ago called Fat Science. It's a very good podcast and they have a very medical lens on metabolism, obesity and related disorders, which of course is amazing. However, I wanted to bring a little bit of what I heard there.

00:29
and sort of understand it through my lens as a nutritionist and someone who has an extensive exercise background and just sort of marry those two worlds together. And the topic is the sex differences in fat metabolism and why men and women store fat differently. So, you you can just picture two people, right? A man and a woman, same body weight.

00:56
Let's say they're the same height, so they've got the same BMI for what it's worth. And on paper, both the man and the woman look metabolically identical. But in reality, their risk profiles are almost nothing alike. He's more likely to be carrying fat around his organs and showing early signs of metabolic stress on the liver. She's more likely to be carrying inflammation and a less favorable cholesterol picture, even though the scales say the same number. And of course,

01:25
This is the thing with scales, right? They give you just one piece of the picture. And so there is this growing body of research trying to explain exactly why these sex differences exist. And I'm gonna walk you through six pieces of that puzzle. What a large clinical data set out of Turkey found when they compared men and women with obesity head to head. What the hormonal explanation looks like. Why your immune system might be...

01:52
running a completely different playbook depending on your sex, and why all of this actually matters for something as serious as cardiac issues. Whether exercise can actually shift these patterns and what role muscle mass itself plays in all of this. So there was a conference earlier this year, the European Congress of Obesity in 2026, and this is not yet published in a peer-reviewed journal article. I went looking for it, but it was presented as a conference abstract.

02:22
at that congress. So it's more like early or emerging research, clearly not settled because nothing ever is. But Piquel and colleagues at Dokuz, iLil University, how's that in Turkey, looked at close to 1200 adults treated at their obesity clinic, roughly 900 women and 250 men. And what they found was that the men in the database had a slightly higher BMI than the women on average.

02:51
which at those numbers BMI is an appropriate tool for comparison and for looking at that, but their waist circumference was substantially larger and their blood pressure ran higher too. They also had significantly elevated liver enzymes, specifically ALT and GGT, which are markers that doctors use to flag early signs of metabolic stress on the liver. So the men were accumulating more visceral fat, the fat that wraps around your internal organs,

03:21
rather than sitting just under the skin and their livers were subsequently experiencing that stress. The women, however, told a different story. Their total cholesterol and LDL ran higher than the men's and their inflammatory markers, things like C-reactive protein and erythrocyte sedimentation rate or ESR, were elevated as well. And these are both signs of

03:50
as I said, inflammation. So instead of that visceral fat and liver stress, the pattern in women leaned more towards that systemic inflammation and the less favorable lipid profile. Now, interesting of course is that these markers don't really dive under the hood intricately to look at actual visceral fat like through an MRI or a dexa, but the waist circumference is a pretty good proxy.

04:16
in a group of this size. Now, Peckle's team pointed to a few likely explanations. Hormones, probably an obvious one, I'm not sure. Immune system differences and where fat physically gets stored in the body. And I just want you to appreciate that while that crude measure of BMI wasn't that different, the actual physiological risk was actually headed in a different direction. And that's the whole reason that I thought this was interesting.

04:46
Weight alone is telling you almost nothing about what's actually happening inside your body. And the fact that there were these divergence that were dependent on sex, I thought was super interesting. So the hormonal explanation, how does a man and woman sitting at the same body weight end up with such different patterns of fat distribution? And we have discussed this before, but I'm going to lead in with the obvious hormonal reason for this happening, specifically estrogen.

05:15
So Lee and colleagues published a comprehensive review in the journal Obesity Reviews in 2025 that pulled together the hormonal and genetic threads behind the sex disparity. And their central finding is one that a lot of us in this health space have, you know, talk about all of the time. Estrogen actively directs where your body chooses to store fat. In pre-monopausal women, estrogen favors that subcutaneous storage, the fat that's just under the skin.

05:45
particularly around the hips and thighs. And it is doing this partly because that kind of fat storage pattern is metabolically more benign and evolutionarily it's thought to support reproductive function. So men who obviously operate with a very different baseline hormonal profile don't get that same protective redirection. Their fat defaults to the more visceral compartment, that deep abdominal fat that surrounds organs like the liver, which is exactly what

06:15
showed up in that Turkish clinic data. And of course, that protective subcutaneous-favoring effect of estrogen doesn't last forever. As estrogen declines through perimenopause and intermenopause, a women's fat distribution pattern starts shifting towards that more visceral, more male-typical pattern. And we've discussed this before, it is one of the most consistent findings in menopause research. And it's a big part of why so many women tell me

06:44
that their body seems to be storing fat differently in their 40s and 50s, even when nothing else about their diet or training or even the scales have changed. And interestingly, estrogen's influence on fat cells isn't uniform across the body. Peterson and colleagues in a paper published back in 2004 showed that estrogen upregulates specific receptors on fat cells, the alpha 2A adrenergic receptor.

07:12
And this receptor's job is to inhibit the release of fat from fat cells. So it stops it. Crucially, these receptors are found in much greater density in the lower body fat, the hips and thighs, than in upper body fat. And if you've ever caught me talking to Brandon about this, he really dives deep into the details about why this matters for things like spot reduction in terms of fat loss. But I digress. So essentially, estrogen

07:42
is telling lower body fat cells to hold onto their fat more tightly, or leaving upper body fat cells comparatively free to release theirs. That's a big part of why lower body fat has a reputation for being so stubborn during a diet, and it's a different physiological reality than what's happening in your abdomen. Now, Gavin and colleagues extended this picture in 2013, showing that estradiol's effects on lipolysis, the process of breaking down stored fat for release, are

08:11
depospecific, meaning that the same hormone produces different effects depending on exactly where in the body the fat cells sit and depend on treatment status as well. So this is part of why generic advice about hormones and fat loss falls so flat for so many women. Estrogen isn't doing just one thing everywhere in your body. It does run differently depending on which location we are talking about.

08:37
And there was a review in Obesity Reviews in 2009 by O'Sullivan, which found that lower body fat exists in a large part as an energy reserve for pregnancy and breastfeeding. And this is something which I'm sure we're quite familiar with, but I'm just completing the picture. It makes evolutionary sense for the body to protect that reserve and make it harder to mobilize under everyday conditions, while remaining more willing to release energy from elsewhere. It's not that your body is working against you,

09:06
It's that it's running on a very old survival program that isn't optimized for fat loss and is in fact only really there to protect reproduction, even if you're not concerned with reproduction. So estrogen's effects don't just stop at the fat cells. There was a review in 2010 by Brown and Clegg that looked at estrogen's central effects or its action directly on the brain on appetite regulation and body weight control.

09:33
largely through its interaction with lectin signaling in the hypothalamus. And on the storage side, Price and colleagues showed back in 1998 even that estrogen regulates lipoprotein lipase, an enzyme that governs how readily fat is pulled out of the bloodstream and stored in a way that specifically limits storage in the lower body. So when estrogen declines, you're not just losing one protective effect, you're losing a coordinated system, appetite regulation in the brain,

10:02
storage limitation in fat cells, and release inhibition that specifically protected lower body fat for over decades. So it's no surprise then that that pattern shifts as significantly as it does. And it's a large part of why women who go through menopause without hormone replacement therapy tend to see a documented rise in visceral fat. While women who maintain estrogen levels through HRT

10:29
may not show the same shift. So when estrogen declines, you're not just losing one protective effect. There's a cascade of things going on. Appetite regulation in the brain, storage limitation in fat cells, and release inhibition that specifically protected that lower body fat for over decades. And you know, it might be a large part of why women who go through menopause without HRT, hormone replacement therapy, they may see this rise in visceral fat.

10:59
While meta-analyses of controlled trials looking at HRT suggests that that HRT may modestly blunt that rise, I will say though that individual trials do tend to disagree on the size of that effect. So this is just interesting and I wanted to sort of bring it to the forefront just because if you've felt that shift in your own body, you know, this is actually a well-documented biological sort of

11:25
underpinning for that. Now it's not just estrogen. Testosterone is also a big part of why men carry substantially more skeletal muscle than women as you know. And on the surface it sounds like there's this clear metabolic advantage for men. More muscle generally means more tissue available to soak up glucose from the bloodstream. But you know it may not be as straightforward as that and in some respects what I'm about to chat about might actually cut the opposite way than you'd expect. And of course

11:55
It isn't just hormones, there are genetic factors at play too. And these have been identified through large genome-wide associated studies that interact with hormonal status to determine an individual's variation in fat distribution. So this is why it isn't just biological difference between men and women that are interesting, but there are very real individual differences between different women going through the same hormonal transition. A really interesting piece of

12:24
this, you know, the differences between the sexes isn't just about hormones and this is about the immune system as well. So there was a published review in Immunological Reviews that looked specifically at how obesity's impact on immune function differs between the sexes. So we know that fat tissue isn't just this passive energy store. It's an active endocrine and immune organ constantly releasing signaling molecules that talk to the rest of the body.

12:54
And this review showed that the signaling looks different depending on sex. So in men, the inflammatory signals coming out of them tend to be oriented towards affecting liver function, which tracks with what was seen in that Turkish data set from the European Congress I mentioned earlier that elevated liver enzymes alongside visceral fat accumulation. And in women,

13:20
that same fat tissue tends to produce signals that lean more towards affecting cardiovascular risk factors, things like circulation and how the body processes cholesterol, which again, lines up with that elevated LDL and inflammatory markers that we've seen in that Turkish population. So part of the explanation here does trace back to genetics rather than just that sort of hormonal difference. Women carry two X chromosomes and a number of immune-related genes

13:49
sit on that X chromosome. That gives women what's sometimes described as a more robust baseline immune response, which is a double edged sword. It's part of why autoimmune conditions are so disproportionately more common in women, because more immune function means that it may be easily more triggered. And in the context of obesity, it appears to be part of why women's fat tissue tends to generate a more pronounced inflammatory signature than men's do.

14:19
at a comparable level of body fat. So really, like when we are talking about sex differences and obesity and fat storage, we're not just talking about where fat physically sits on the body. We're talking about these different sets of downstream biological consequences mediated by hormones and the immune system. And it looks to be different in men and women, even when the numbers on the scale or the tape measure do look the same. So if we're thinking about heart health then,

14:48
There was new research presented at the American Heart Association's Lifestyle Scientific Sessions in Boston in March, 2026 that looked specifically at the relationship between central obesity, fat stored around the waist and heart failure risk. Like the Turkish data, I will say this is a conference abstract. It has yet to be a peer-reviewed published paper, so it's preliminary. The study itself was well-designed and it drew on

15:17
a long-term data set called the Jackson Heart Study, which followed nearly 2,000 African-American adults in Mississippi for almost seven years. So the researchers Chen and Cheng found that waist circumference and waist to height ratio protected heart failure risk. BMI did not. So effectively, the overall number on the scale really didn't tell you anything useful about a person's future heart failure risk, but where their fat was stored,

15:46
did tell you a great deal. Over the follow-up period, 112 people in this study developed heart failure. And when the researchers dug into why waist circumference was such a strong predictor, inflammation turned out to explain roughly a quarter to a third of that relationship. So in other words, it wasn't just that visceral fat was mechanically pressing on organs or anything like that. It was actively generating an inflammatory signal.

16:14
that appears to contribute directly to heart failure risk. And of course, that comes back to that idea that fat tissue behaves like an active immune organ rather than just being this sort of passive padding. So like an obvious limitation that's worth chatting about is that this particular study population was single race, single region cohort. So we can't assume that exact magnitude of that relationship generalizes perfectly to every population.

16:44
But again, that core finding that where you carry fat predicts cardiovascular risk is pretty consistent with a much broader body of literature. And particularly in women who are moving through perimenopause and menopause, whose fat distribution is actively shifting in that more visceral direction. And heart-related outcomes aren't as well recognized in women than they are in men. And a lot of the risk factors look different.

17:11
So I want to just briefly talk about muscle mass because earlier I flagged that testosterone drives men's higher skeletal muscle mass and that this looks on the surface like a straightforward metabolic advantage. Gardeau and colleagues in 2024 review of sex-based differences in insulin resistance confirmed something that I think surprised a lot of people. So women are generally more insulin sensitive than men despite having less muscle mass.

17:39
and that advantage holds right up until menopause, at which point it gradually disappears. So less muscle isn't translating into worse blood sugar control for women, and it isn't just the estrogen that is responsible for that insulin sensitivity. Nicolaeson and colleagues in 2024 compared men and women matched for age, BMI, and fitness, and they found that women's fat tissue and muscle tissue

18:07
both showed a greater molecular capacity for taking up glucose, more of the actual transport machinery, things like Glut4 transporters were present at that cellular level. So their conclusion was that the superior cellular efficiency compensates for women having less total muscle mass to work with, which is pretty interesting. I would have thought that

18:32
estrogen was largely responsible for that insulin sensitivity and this is one of the reasons why we were more sensitive. But no, it's actually having more of that transport machinery to be able to take that glucose up from the cells. So that was pretty cool. But of course, muscle mass isn't irrelevant. It just plays a more specific role, I guess, than having this sort of blanket metabolic advantage for whoever has more of it. Radha-san and colleagues in an

19:01
earlier study out of Thailand found that women's higher blood glucose readings after a meal were substantially explained by their smaller, lean muscle mass specifically. But once that was accounted for statistically, the sex difference in post-meal glucose response largely disappeared. So clearly muscle mass does matter for certain specific metabolic outcomes, but it isn't just the single most deciding factor in overall insulin sensitivity the way that I assumed it was.

19:30
And Goossens and colleagues in a 2020 review described cardiometabolic health as something that emerges from the combined interacting effects of fat distribution, muscle metabolism, and liver function together, rather than any one of these acting in isolation. So I think that's really the theme of this entire episode, is that these sex differences exist, and it's to do with fat storage, hormones, immune signaling,

20:00
and muscle tissue itself, and they interact together. So when we discuss differences between men and women from a cardiometabolic health perspective, from a body fat distribution perspective, and why things change as a woman heads from reproductive age into perimenopause and menopause, you can see that it isn't just one thing that's shifting. There is a cascade of things which interact

20:30
and are responsible for the overall outcomes. And of course, none of this is irretrievable because clearly your habits around diet, exercise and lifestyle will overlay any of these sort of physiological challenges that occur based on sex and will steer your sort of health journey in any direction. But left on its own with no changes, hopefully this gives you some insight into why you might see changes that you wouldn't have seen

20:59
10 or 15, or maybe even five years ago. Anyway, if nothing else, just know that the number on your scale or the body mass index BMI at that individual level is just not that useful. It's just not very useful information to give you insight into your metabolic and cardiovascular risk health. Weight circumference is important. Your habits and lifestyle are important, obviously. And where that goes,

21:27
arguably is more important than how much body fat you store overall. Alright team, that's what I've got for you. I'd love to hear any thoughts. You can catch me over on threads, X or Instagram @mikkiwilliden, Facebook @mikkiwillidenNutrition, or head to my website, mikkiwilliden com. Scroll right down to the bottom, pop your name in the box and jump on my email list. You guys have the best week. See you later.