- ChREBP plays a key role in the control of lipogenesis through the transcriptional regulation of lipogenic genes, including acetyl-CoA carboxylase and fatty acid synthase
- Liver-specific inhibition of ChREBP in ob/ob mice markedly improved hepatic steatosis by specifically decreasing lipogenic rates.
Obviously we need to be careful here because we are dealing with ob/ob mice, but the message is clear, ChREBP induces lipogenic gene expression. No doubt this is partly responsible for the fatty liver in ob/ob mice as demonstrated in the last bullet point above. The point I want to deduce however is that, if ChREBP favors "lipid accumlation" in the liver, what do you think ChREBP is doing in the adipose tissue? Surely it must favor lipid accumlation there aswell??! I.E. OBESITY.
I must be mad to think this right?
The only conundrum I have to contend with is the study in Lucas Tafur's post which showed that obese people have reduced levels of ChREBP in adipose tissue compared to lean people. Such confusion! But perhaps this phenomenon is observed because the obese people are already fat. It should stand to reason that for a given particular individual, their potential to get even fatter is steadily reduced as they fatten up. In this situation it makes sense that adipocyte ChREBP would decline as they become obese.
We also have the notion from the study I linked in my previous post, this one, they showed that per adipocyte, glucose uptake is less in obese people compared to lean people. BUT, and here is the punchline, this is over-compensated for by the fact that obese people have more total fat tissue. This fits in with the above idea that adipocyte ChREBP is reduced in obese compared to lean.
Something else just clicked this morning aswell..... remember how I posted that fat issue growth drives over-eating, and NOT the other way around? ( 1 ) Well check out this study again.....what does Troglitazone do? We established last post that it most likely encourages fat tissue growth, no wonder the people taking Troglitazone reported increased hunger. duh!
I want to bookmark some studies below that I will look into in the coming days. If I find something interesting ill make a post!
Hidden variant of ChREBP in fat links lipogenesis to insulin sensitivity.
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha.
On the role of liver X receptors in lipid accumulation in adipocytes.