Well, I guess we all knew what we eat affects our health but I didn’t know that obesity was the second leading cause of cancer behind smoking. In other words, obesity is the leading cause of cancer in non-smokers – at least according to this research:
Perhaps I’m lost in some kind of time warp but this clear link is news to me. I can’t find the relevant Nature magazine article online so whatyaallthunk - anyone aware of any available research on the subject ?
The recognition of a link between obesity and certain cancers is actually not that new. For example, IIRC, obese women have long been known to be at risk for breast and uterus cancer. Although certain dietary factors may be at work in this regard (eg. high fat diet), another plausible explanation for the link between obesity and such hormonally influenced cancers is via estrogen. Simply put, estrogen is made in fat tissue. The fatter you are, the more estrogen you produce (regardless of your sex). So, tumors promoted by estrogen are more likely to develop in obese people.
The link between obesity and various non-hormonally influenced cancers, such as kidney or bowel cancer, is less clear. One explanation may lie in the presence of high levels of either insulin itself or what are called “insulin like growth factors” in many obese people. Insulin like growth factors, especially, may promote tumor growth. As mentioned, these factors (and/or their effect) are more prominent in the obese.
KarlGuass–“Simply put, estrogen is made in fat tissue”
Estrogen produced by the adipose tissues? OKay. I understand that you’re an endocrinologist, but I’d like to see the Northerns and Westerns that support that claim. References, please. Classically, estrogen is produced by the female gonads. (and the male). I’m sure you can back it up, I’m interested.
An interesting topic of discussion going on in the department that I work in at is that adipose cells are an under-recognized hormone producing cell type. One postdoc claims that in a few years, we’ll see see more hormones from the adipose than any other tissue type, blowing away the pituitary.
Estrogens refer to a class of steroid hormones with similar biologic effects but differing activities. The most potent, estradiol is produced in the ovaries. Another estrogen, estrone is produced in fat tissue by the action of an enzyme found in adipose tissue called aromatase. This enzyme transforms androgens, originally produced in the adrenal glands, into estrone. So, in truth, the adipocytes don’t synthesize estrone de novo but rather make it from a closely related steroid precursor that’s been delivered to the fat tissue.
The production of aromatase in adipose tissue occurs because of a tissue-specific promoter for aromatase found in fat. The needed promoter is not found in other tissue in any appreciable quantity except, IIRC, placenta and, of course, the ovary.
I don’t have any reference off the top of my head with respect to the techniques used to assay the promoter, its response elements, etc. A web search using “promoter” and “adipose” and “estrogen” gives lots of hits but most need Adobe downloads and weren’t easy to link.
Thanks for the links, gigi. Very informative stuff. Without getting too graphic, one can see the reasoning in a link between diet and prostate cancer (usually in men)…obviously, a lot more research is being done on other areaas. Cheers.
Aromatase promoter?
You are going too far neglecting the principles of endocrinology.
Fat cells contain primarily fat (what a concept). Steroids are fat soluble compounds. By default, fat tissues exhibit much higher steroid content than any other tissue. In addition, fat cells infiltrate all parts of our body making them available to all forms of cancer.
More simply, the more fat you got, the more steroids are available to cancer cells.
BUUUUUUZZZZZZZZZZZZZZZZZZZZZZZ
Wrong answer, but thanks for playing.
KG has it 100% right. Fat cells do produce hormones with estrogenic activity.
If the primary effect were due to storage of estrogen by fat cells as you suggest, obesity should produce a hypo-estrogenic state. Think about it. Estrogen that’s sequestered in a fat cell can’t get to a breast ductule or endometrial cell. Even if a chock full o’ estrogen fat cell is immediately adjacent to a breast ductule, it won’t passively release a drop of estrogen. In fact, if your notion was correct, fat would serve as an estrogen sponge. Although, perhaps estrogen is released with adipose tissue breakdown secondary to fat mobilization.
For an early in vitro study of the production of estrogen by adipose tissue try this link
“We conclude that the ability of human adipose tissue to form estrogen is not a function primarily of the adipocytes but rather resides principally in the cells of the stroma.”
It will show you that the main source of estrogen is the ovary and estrogen content in fat is highly correlated with the state of the estrous cycle. Fat cells are the main storage of steroids in the body. The fatter you are, the
more estrogen you retain. Fat does serve as an estrogen “sponge”. When fat releases triglycerides, steroids are also released.
In the future, when you making homorous comments you should first be sure that I’m wrong.
dasmoocher: The links are interesting (although the last one refers to breast adipose tissue, which is not the subject here).
Still, the paper you cite states that the aromatase mRNA levels are higher in adipose stromal cells than in the adipocytes. The levels are still non-zero in the adipocytes.
Regardless, we are getting into semantics. I used the terms adipocytes and adipose tissue interchangeably, and that was imprecise of me. Bottom line is that estrogens are synthesized in adipose tissue. You still seem to be viewing adipose tissue as some sort of passive estrogen sponge. I disagree. The adipose tissue actively synthesizes estrogens.
(BTW, if the sponge concept is valid, why doesn’t the adipose tissue accumulate androgens and all the other steroid hormones?)
I apologize for the remark. You raised my ire with your post, however, when you began replying to Karl Gauss’ post and said:
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KG has a very solid reputation for posting accurate information and considered opinions. Additionally he, is an endocrinologist IRL. I’m not saying build a shrine to the guy, but give him the benefit of the doubt.
Back to science. You posted:
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Those stromal cells are part of the adipose tissue I referred to in my post, no?
Then you posted:
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The abstract stated that obese women had normal levels of E1 and E2, but lower levels of acyl-estrone. A quick search on acyl-estrone brings up papers that discuss its role in weight regulation, but not its estrogenic activity. Does it have any?
Finally, you posted:
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When I read the abstract, I came across this:
Bolding mine. I interpret this as implying that in post-menopausal women (where ovarian estrogen production is minimal) there is:
still a great deal of estrogen and some of it gets socked away in fat
the amount of estrogen is proportional to obesity (this suggests that the estrogen originates from some tissue you have lots more of if you’re fat).
the E1/E2 ratio is elevated in the adipose tissue of post-menopausal women.
What I have yet to see is any evidence for is whether there is some signaling mechanism that promotes selective mobilization of hormones from adiptocytes. Such a scenario makes more sense that co-mobilization of estrogens with triglycerides since energy demands and estrogen demands are not intrinsically linked.
Thanks KG as to aromatization by fat tissue; this makes some sense. Although I still understand the classic model of estrogen production is that androgens are first synthesized by one type of cell (thecal) in the female gonads and then aromatized by another cell (granulosa) type by aromatase. This produces the ~vast majority of estrogen in the body.
The adrenal also produces some sex steroids, in addition to glucocorticoids and mineralocorticoids; but, isn’t most of the estrogen formed by the ovary, and not adipose? I think this is what dasmoocher was trying to say with his links.
choosybeggar–Looking at links and KG’s response, it seems we are bogged down in sematics. Adipose tissue that includes vascular and stromal cells might not be considered adipocytes (the actual fat cells). Pituitary tissue would be positive for all types of pituitary hormones; but there are several identifiable cell types within the pituitary. How do you differiatate somatotrophs from gonadotrophs if you are looking at gross pituitary tissue? Saying aromatase is found in fat tissue is a little undefined, isn’t it?
A personal speculation (I don’t have time to research this, but off the top of my head) as to fat as an estrogen sponge and as not an androgen or other steroid ‘sponge’–wouldn’t the fact that estrogens are aromatized, and other steroids aren’t, make estrogens more lipophilic than other steroids?
Just to clarify. I posted that estrogen was synthesized by adipose tissue. Dasmoocher seemed concerned that the bulk of the synthesis was confined to adipose stromal cells and not the adiptocytes themselves. I reiterated my claim which, while not specific (as you point out), is accurate.
In terms of this discussion, which cell type in fat makes the estrogen is irrelavant, as long as there are more of these cells in obese individuals.