Dr. Betty Murray explains why menopause makes weight loss harder: dropping estradiol reduces insulin sensitivity in muscle, impairs glucose uptake, and shifts your metabolism toward fat storage and away from fat burning. Calorie-cutting and exercise become far less effective.
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Foreign so insulin signaling estrogen declines. Right? Estrogen declines as we enter into perimenopause and it directly impairs insulin sensitivity in the, what they call the peripheral tissue. So this is your muscle tissue, especially skeletal muscle. So these are the big groups, your hips, your thighs, your buttocks, your abdominal muscles, your back muscles. This is where insulin mediated glucose uptake is normally doing the heavy lifting. So let me say that again. In order for your body to burn carbohydrate glucose appropriately, the majority of it is happening in your skeletal muscles. So if you're like I am and you spend an inordinate amount of time sitting on your butt because you're working all day, you are not burning a lot of your actual glucose through skeletal muscle activity. So inactivity is going to increase this. But perimenopause does a number on your AB ability for your skeletal muscles to use glucose. Decreases in estrogen affect a particular estrogen receptor. So we have estrogen receptor A and estrogen receptor B. Now both of these are important, so it's not like you want one and not the other. And all of your tissues have estrogen receptor A and estrogen receptor B. What's interesting is estrogen receptor A when it is properly estrogenized. So think of it as estrogen's the key the receptor, it goes in and clicks in when A gets properly stimulated, not too much, not too little. We get better insulin sensitivity when we start to lose estrogen activity. Or it's wildly varied. What we see is insulin resistance and that is independent of changes in your body fat. So that is independent. So, so estrogen activity is going to change the alpha receptor of estrogen and its ability to stimulate muscle utilization of glucose. So the independent of adiposity or fat is really important because it implies that insulin resistance and its menopause related activity is not just about weight gain, it's actually direct. And during the menopause transition, this hypoestrogenic state is worsening insulin resistance at these big muscle groups and compounding increased adipose adipocyte activity. So increased fat building. Right? So not only are we not burning, but we're going to see an increase in, in adipose tissue, fat tissue, and that causes lean muscle mass reduction. All right, so skeletal muscle can't do its job and it's the estrogen receptor A that's the primary driver. So estrogen way too high drives insulin resistance, estrogen way too low drives significant estrogen resistance. And then so the skeletal muscle can't burn fat and sugar and it can't burn very efficiently. And we get cellular resistance and increased fat building and fat production. So when estrogen declines, we also get increased insulin production by pancreatic B cells. And so we see less disposal of glucose and use of insulin in the muscle and more insulin production by your pancreatic cells. Now, this becomes problematic because that means you have more sugar outside the cell in the bloodstream hanging out, waiting to get burned. So why is that important? If you have glucose sitting outside the cell waiting to get burned, your body's not going to flip the switch and go, hey, I'm going to burn fat, right? It's a seesaw. We have to have. We have to have utilization work really well, and we don't want a bunch of glucose sitting out in the street waiting to get burned. Now, Glute 4 is one of the transports that takes glucose once insulin has pushed it across the cell wall and helps transport to the mitochondria that translocation during menopause are limited. And this is part of the impaired insulin secretion and sensitivity. And it strongly suggests that GLUT4 disruption is a trafficking mechanism that actually slows the ability of GLUT4 to sort of take glucose to the powerhouse. So ultimately, what happens is you can't get it into the powerhouse, your mitochondria. So what happens to a cell when I've got glucose sitting outside the mitochondria, not getting burned, it can get burned in the cytosol, right? And that produces lactic acid, and we get much less energy production. But the other thing is that starts to create sort of a cytotoxic, a glucotoxic situation inside the cell, and it becomes less capable of doing its job. So take home message. Your transporter from taking it from insulin to take your glucose to the powerhouse gets impaired, and this starts to compound that metabolic effect of perimenopause. Now, our mitochondria, our powerhouses, our powerhouses do several things when it comes to fat. So fat is burned through an activity called beta oxidation, and that starts to slow down during perimenopause and menopause. Our ability to produce ATP, your actual energy molecule, has been turned down because of the mechanisms that are affected by glucose. But it also gets turned down to your ability to use fat through beta oxidation to create ATP and we increase lipid synthesis. So that's a fancy way of saying lipids, I. E. Producing fat by the liver to be stored in your fat cells. So on the mitochondrial side, estradiol loss is associated with A downregulation with the genes that increase fat burning through beta oxidation, which. Which basically malfunctions the entire act of using excess free fatty acids for energy. So what does that mean? If your body was successful in moving fat out of the fat cell, dumping it into the bloodstream to get burned, which requires glucose to not be sitting out in the bloodstream, at least not in high levels. There's always some glucose, but if we have a lot of glucose, our body is going to use that first. So even if fat is sitting in the bloodstream, it requires beta oxidation and epinephrine to get into the mitochondria. So EPI is the major driver of that activity. But the genes that then take it and say, cool, I'm going to take it to the powerhouse. The mitochondria, which is the only place fat can get burned, aren't doing their job very well. So we basically become less capable of producing energy, ATP from body fat, and we just can't produce that much. So instead of being a Lamborghini, we are now in 1987 Yugo. So we become very slowed. So if my goal before was I'm just going to cut a few calories, work out a little bit more, and burn fat on a cardio machine, I am, I am basically trying to climb the Himalayas with a pickaxe in. In a bathing suit and running shoes. It's going to be real hard.
