What is required for obesity?

This post is something of a reply to Guyenet's latest post, whereby he ends with the line "and it certainly does not erase all previous evidence suggesting that hyperinsulinemia isn't required for obesity"

This is true, and is actually obvious.

Obesity is the accumulation of excess numbers of adipocytes, and excess adipocytes can only occur in the presence of adipocyte multiplication also called adipogenesis or simply fat tissue growth.

So whats the controller of adipogenesis?

Well, so far the research has pinpointed the transcription factor PPARγ as the "Master regulator" of adipogenesis. Without PPARγ precursor cells are incapable of expressing any known aspect of the adipocyte phenotype.

Also check out this line from this abstract.....

PPARγ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes.

That part I bolded should be sending off some alarm bells in your head now with regards to PPARγ. Theres no question, if you want to get fat, just stimulate the PPARγ transcription factor inside your adipocytes....

So the next question is, what controls PPARγ in adipocytes??????????????????????

Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes

With this line.....

In explants of human adipose tissue, PPAR-gamma protein levels were significantly increased (42 +/- 3%, P < 0.05) after 12 h of incubation with insulin

That sounds something like hyperinsulinemia to me, and if hyperinsulinemia increases PPARγ, you can bet your ass that hyperinsulinemia can make you fat. The point though is that it is the downstream affects of insulin acting on the adipocyte to stimulate PPARγ that fundamentally produces obesity. Hyperinsulinemia in and of itself will be useless in producing obesity if its not hitting adipocytes and/or stimulating PPARγ.

Its very likely the FIRKO mouse cannot get fat because it cannot stimulate PPARγ inside its adipocytes.