Friday, 28 September 2012

Adipocyte ChREBP

ChREBP is something that Lucas Tafur talked about here. His post is a good primer on the subject of ChREBP but beware its quite a technical post.

Anyway, to simply put it, ChREBP is how your body REACTS to dietary carbohydrate. The picture in Lucas's post is such a fantastic illustration of exactly what "life" is.

"life" is quite simply dead pieces of matter REACTING to their environment. The reaction is usually always predictable and the same, which is why I am a strong believer in determinisim and why I refute the idea of "free will". .Anyway, I stumbled on quite a few interesting things involving ChREBP and its quite likely that its one of the important technical things missing in Taubes's Carbohydrate Insulin Hypothesis.

Troglitazone is an anti-diabetic drug that is used to "treat" diabetes. Essentially what this drug does is instruct your adipose tissue to get very good at sucking up blood sugar and converting it to fat, thereby helping to control hyperglycemia  Troglitazone has the well known side affect of weight gain. But how exactly does Troglitazone enhance glucose disposal in adipose tissue? Well, either it enhances adipose tissue glucose uptake OR it promotes adipocyte differentiation ( or probably some combination of the two ). Initially I thought it was the first option, which lead me to search for studies which showed that Troglitazone increased leptin, since we already know leptin secretion is a product of carb to fat lipogenesis.

So if I could find a study that showed Troglitazone increased leptin that would be pretty good evidence that Troglitazone increased adipose tissue glucose uptake, but instead what I found was this. This study says that Troglitazone decreases leptin in patients with BMI less than 30 but leaves leptin unchanged in patients with BMI over 30. This leads me to the conclusion that Troglitazone works primarily by adipocyte differentiation, probably with some secondary affects of increased adipocyte glucose uptake.

However, one thing we can be sure of though is that Troglitazone increases adipocyte ChREBP. ( 1 ) And Troglitazone makes you fat. So.........anything else that increases adipocyte ChREBP likely also makes you fat........... what else increases adipocyte ChREBP? Yes baby thats right, glucose + insulin. Another point made by that paper is this.....

ChREBP expression in adipose tissue is not significantly affected by the diabetic state

Once again, this leads me to conclude that diabetes is a manifestation of the adipose tissue failing to expand to accommodate for increased glucose uptake, i.e. your adipose tissue does not want to act as a sink for excess blood sugar during hyperglycemia. On the other hand, if your adipose tissue is happy to expand and suck up excess blood sugar, youll get fat instead of getting diabetes.

BTW, maybe its just a coincidence that one of the downstream targets of ChREBP is fatty acid synthase, and that some cancer's are associated with over-expression of fatty acid synthase. Cancer is also associated with metabolic symdrome......... But yeh,.....anyway....... its probably all just a coincidence. Probably.

Now, for some funny reason, I cant seem to find this study in pubmed...

analyses of adipose tissue lysates revealed greater fatty acid synthase (FAS) and acyl-CoA carboxylase expression in the HC fed groups, suggesting increased de novo lipogenesis following HC consumption. Increased lipogenic protein expression was also associated with greater nuclear levels of carbohydrate-response element binding protein (ChREBP) in HC fed rats.

And here's a brand new study looking at ChREBP in fruit flies! ( 2 ) You dont need to read the study or even the abstract, because the title tells you everything you need to know.....
Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila.

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