47: The Skinny on Fat - Sex and Fat Metabolism with Dr. Ben Bikman

Hello and welcome to this week's episode of the metabolic classroom through insuliniq.com I appreciate, as always, the fact that you're joining me. I'm delighted to be able to be your professor again for another classroom. Today we are continuing our theme focusing on fat tissue. Fat tissue. What I've hoped to impress upon you by now is that it is far more than simply an inertia tissue that only acts to store energy for later use. While that is certainly an important part of it, today we're really exploring an oft overlooked aspect of adipose tissue, namely its role as an endocrine organ. Now, you've heard the term endocrine organ before, I'm sure, and if you haven't heard that term, you certainly are familiar with the classic endocrine organs. These are the glands within the body, the tissues that produce hormones and release these molecules into the bloodstream to have effects throughout the body. And some of the more famous endocrine glands are things like gonads, ovaries and testes, or the thyroid gland or adrenal gland. Adrenal glands. All of these are tissues you've heard of before, and they're famous because they are releasing their energy or they're releasing molecules into the, into the bloodstream. Now, some of these are inert from various tissues or only have a modest effect. And then some, the ones that are coming from fat tissue have, or each. Let me say that all another way. Each endocrine organ has hormones that will have very specific effects relevant to that tissue's function. And the fat tissue is related to metabolism. And so it's no surprise that its hormones have a metabolic influence. And that's really what I'm going to share with you as we go through some of the specifics of the hormones. But some, a couple that I'm going to mention, appear to not influence metabolism and have very, very unrelated effects. All right, so some of these, the hormones that we're going to cover, as I mentioned, they're going to include ones that are, are overtly metabolic in theme, like leptin. But then there are going to be others that are less metabolic and more pertaining to, say, sex, because fat tissue has a surprisingly important influence in sex hormone production at certain times of life, and we will cover that. But hint, it has to do with menopause. In fact, with menopause in mind. Let's just start there. As we start talking about the endocrinology of the adipose tissue. Men and women are, are not the same. And we store fat in Very different places. Now last, in the previous episode, we discussed why men and women store fat differently. And it is entirely a function of sex hormones, where the sex hormones induce the expression of lipoprotein lipase in different fat DNA depots throughout the body. For example, just as a brief recap, the higher estrogens in the woman or the girl who's going through puberty result in higher expression of lipoprotein lipase at the prototypical female areas like breasts, hips and buttocks. Whereas the androgens like testosterone, which are much higher in the boy, the male going through puberty, they that begins expressing more lipoprotein lipase in the central region of the body, leading to greater abdominal and even visceral fat storage. Now, we store fat in different places between the two sexes, and those different depots have differing effects on on hormone production. So for example, in women, because women have relatively much higher levels of subcutaneous fat, it's no surprise that she will have relatively higher levels of the hormone products that come from subcutaneous f. And these. And I'm going to go into the details of these hormones in more in more complexity in just a bit. But for example, she will have higher levels of hormones like adiponectin and leptin, which are much more abundantly produced from subcutaneous fat cells than her male counterparts. Whereas the male, while having relatively lower levels of those hormones from fat cells, will have relatively higher levels of hormones or signals that are coming from central or even visceral adipocytes like TNF alpha. Now, TNF alpha, we, we are justified in calling it a hormone, but it also meets another characteristic and it is also called a cytokine. A cytokine, that is the term to refer to these proteins that influence inflammation and immune functions. So where we have more visceral fat, we're going to be producing relatively less of hormones like leptin and adiponectin. And we're going to go into a much longer list in just a moment and then more, relatively more of the pro inflammatory signals. And there's even another one that I'm going to mention in a moment. So where we store fat, which is heavily influenced by our sex, will also then in turn heavily influence the production of hormones. Now let's just talk a little bit more about menopause. Menopause is a unique change in the woman's certainly her fertility, but as a result of that change, her hormone production. So the main cells of the ovaries that are producing sex hormones are the granulosa cells and the theca cells, and they normally will ex ob, they will proliferate or you'll have much more of those cells surrounding follicles, which is a little egg, kind of a wrapped up egg within the ovary. And during menopause, as she transitions into menopause, it's essentially her ovaries running out of follicles. As the ovary runs out of follicles, it's no surprise that the relative amount of granulosa cells and theca cells, which again are the two cells that are producing sex hormones, is diminished. So not only does this result in the ovary actually shrinking, it does get smaller. But the relative composition of the ovary so the cells that make up the ovary starts to shift somewhat. And as the granulosa and the theca cells go down in number, other cell types like fibroblasts go up. Now, a fibroblast is really the cell type of connective tissue and even scar tissue. Now, that's not to say that the ovaries are becoming, are becoming a little more fibrotic, so a little less functional. And in that stage, the main source. So the ovaries. Normally, we've talked about this abundantly before, but it's very relevant to this lecture today. The, the, the ovaries are very involved in this process called aromatization. Aromatization is a. It's admittedly an unfamiliar word, but it refers to this process of converting androgens to estrogens. And I am deliberately using the plural, you know, creating estradiol from testosterone, creating estrone from androstenedione. So taking androgens, the prototypical male sex hormones, and converting them into estrogens, the prototypical female sex hormones. After all, all estrogens were once androgens. You cannot get to estrogens without first passing through the androgens. And to do that, to actually make that conversion, you need this enzyme called aromatase, which is why we've turned it into a verb and say that we have this process of aromatization. So ovaries are good at aromatizing androgens or converting testosterone to estrogens, if you will. Now, as the theca cells and the granulosa cells are reduced in number with menopause, there's less androgen production and thus less aromatization happening in the ovaries. In this stage of her life, most of her androgens actually are now coming from her adrenal glands, which is a topic for another time because it is its own beast. So the adrenal glands become the primary source of androgens in her body. Now still, they need to be converted to estrogens. And this is where the fat tissue comes in, because in the postmenopausal woman, the fat tissue is the main source of estrogens. Now, it's not making them from scratch. Remember, the fat cells are simply pulling in the androgens and in this case the androgens that are coming from the adrenal gland and converting them into estrogens. So I'm just going to repeat all of that because it's a fascinating change in her body as the ovaries become less active. Not that they're gone and not that they're not contributing at all. They still are, but they're no longer the primary source of sex hormones. Most of her androgens, like testosterone, are now coming from her adrenal glands rather than her ovaries. And then most of the androgens are getting converted into estrogens are happen. Are doing so in the fat cells rather than the ovaries where they used. Where it used to happen. So her fat cells in the female with menopause are very, very important in this process. All right, so again, this just to just to remind you, the overall topic is us talking about the endocrinology of adipose tissue. And here it is very, very relevant because the adipose becomes the primary source of estrogens in the postmenopausal body. Now, I somewhat touched on this. As we transition into the next.