Thanks to libgen I got my hands on this paper which seeks to more closely examine the contribution of hyperplasia to obesity. ( basically hyperplasia is "recruitment of adipose progenitor cells" ) Normally adipose tissue is riddled with stem cells......( also referred to as fibroblasts etc ) .... think of them as building block cells.
These cells have most of their DNA coiled up tightly around the nucleosomes such that hardly any gene's are expressed, which means they essentially have no phenotype. Then, for whatever reason, at the on-set of obesity, these cells receive the message to differentiate into fully mature adipocytes, the DNA for the PPARg2 gene is uncoiled from the nucleosome, the activity of the triglyceride synthesizing enzymes increases many-fold, and the cell starts accumulating fat.
Here are some quotes from the paper.......
recent studies have found that adipocyte hyperplasia plays an important role in human obesity5,6. Specifically, obese individuals have significantly more adipocytes than lean individuals, and this trend is maintained throughout adult life5.
Even after obese individuals undergo severe weight loss, elevated adipocyte number is maintained5, indicating that increased adipocyte formation in obesity has lifelong effects on adipose tissue homeostasis and WAT mass.
In the study, they put mice on chow and HFD's and looked at when recruitment of pre-adipocytes occurs with respect to obesity development. Surprisingly, pre-adipocytes start to get activated within 1 day of HFD exposure, peak at 3 days, and returns to baseline at 5 days. ( although it takes 7-8 weeks for them to fully differentiate into adipocytes and store fat, it seems you can get the "ball rolling" extremely quickly, i guess I need to think carefully next time before I indulge in a cheat meal...........)
Perhaps the most interesting part of the study is what they found when they tried to determine the pathway's involved in the activation of pre-adipocytes. They focused on the phosphoinositide 3-kinase (PI3K)-AKT pathway ( which is downstream of insulin ) . Specifically, they looked at AKT...
The AKT kinases regulate several processes, including cellular growth, survival and metabolism29. The most prominent mammalian isoforms are AKT1 and AKT2. Whereas AKT1 is widely expressed and promotes the growth of many tissues30,31, AKT2 regulates metabolic flux within liver, muscle and adipose tissue
They found that after several days of HFD exposure, AKT1 was unchanged while AKT2 was elevated, which led them to speculate it was AKT2 that got the pre-adipocytes ready for differentiation. Next they knocked out the AKT2 gene specifically in adipose tissue. The Akt2(-/-) mice actually developed normally with normal body fat levels, and as expected, were resistant to weight gain and adipocyte hyperplasia when fed a HFD.
This actually has profound implications, it suggests that the "new bodyfat" you develop in obesity is different and distinct from your "normal" adipose tissue that you get from birth and when growing up. Obesity is like an addition of a "new" type of adipose tissue, it is not merely the expansion of your normal fat mass, but a completely new beast altogether....
Although the formation of adipose tissue in development,.... and the expansion of adipose tissue in obesity..... are often viewed as temporal variations on the same regulatory process, we show here that the formation of adipocytes in obesity and development are controlled by distinct molecular mechanisms. The existence of an aberrant mechanism of adipogenesis in obesity supports the American Medical Association's classification of obesity as a disease
What happens to an ob/ob ( leptin deleted ) mouse that is also akt2(-/-) ? ....Yes, they are also resistant to fat gain, further indicating the importance of hyerplasia in obesity development.
Our data suggest that even relatively short binges of altered eating behaviour may stimulate obesogenic adipogenesis, resulting in an intractable increase in adipocyte number5 that may make future weight loss more difficult.
The only caveat to mention is that almost all the hyperplasia was detected in the visceral depot with only small amounts in the subcutaneous depot. I would extrapolate this with caution to humans however, and im pretty sure the subcutaneous depot undergoes massive hyperplasia in human obesity, I mean you dont think a panniculus is due to hypertrophy do you? Or that all that excess skin is "just skin", and not billions of shrunken hyper-plastic fat cells......