America has been growing in a bad way, getting fatter and fatter over the last 30-plus years. Perhaps it is no coincidence that this occurred during the time when doctors and dietitians were telling everyone to eat low-fat diets that replace fat with carbohydrates. Research, such as the study reviewed herein, suggests that limiting the exposure of fat cells to insulin is a vital first step to controlling and managing weight. It may not be a popular message with grain producers, bakeries and confectionaries. For the health of America, it is important to realize the dangers and long-term consequences of succumbing to the temptation of tasty treats. Sadly, the audience most receptive to this message will be athletes and fitness enthusiasts who are already exercising and following a sensible diet in order to maintain a level of performance or physical appearance.
For those of you interested in how many different steps in the breakdown and release of stored fat that are inhibited by insulin:

• High concentrations of insulin disrupt the close apposition of ß-receptors with protein kinase A (PKA).
• Insulin increase phosphodiesterase 3B concentration, inactivating cAMP.
• Insulin inhibits the activation of PKA by cAMP or its phosphodiesterase-resistant analog, 8-bromo-cAMP.
• The insulin-based inhibition of PKA signaling results in markedly reduced phosphorylation of perilipin, which reduces the exposure of triglycerides to hormone sensitive lipase (HSL).
• The insulin-based inhibition of PKA signaling results in markedly reduced phosphorylation of HSL, reducing the lysis of triglycerides to free fatty acids and glycerol.
• The insulin-based inhibition of PKA signaling results in markedly reduced phosphorylation of CREB, which results in a marked reduction of mitochondrial biogenesis in the adipocyte.


References:
 
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6.     Holm C, Osterlund T, et al. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Ann Rev Nutr, 2000;20:365-93.

7.      Hoeks J, van Baak MA, et al. Effect of beta1- and beta2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP-3 expression in humans. Am J Physiol Endocrinol Metab, 2003;285:E775-82.

8.     Kaaman M, Sparks LM, et al. Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue. Diabetologia, 2007 Sep 19;[Epub ahead of print].