Insulin sends strong signals to the body to store fat in a range of tissues. Too much insulin circulating in the bloodstream is known to lead to accumulation of adipose tissue.
At the same time, mice with reduced insulin have increased energy expenditure. A team led by Jim Johnson established this seeming paradox in previous work, in which the underlying mechanisms remained unclear. In a study published today in the American Journal of Physiology, Endocrinology and Metabolism, visiting fellow Dr. J Diego Botezelli, Dr. Johnson and colleagues investigated the effects of genetically reducing insulin production on uncoupling and oxidative mitochondrial proteins in liver, skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT).
“Here, we asked whether Ucp1 or Oxphos proteins [which are both modulators of mitochondrial metabolism implicated in the development of both insulin resistance and insulin insufficiency, and associated with type 2 diabetes] might be altered by circulating insulin and diet,” Dr. Johnson posted in a tweet.
“The answer is yes,” added Dr. Johnson, “but it depends on what tissues you look at, and even what type of adipose tissue (one of the main early insulin target tissues).
“Collectively these data show that, early in life, lower circulating insulin levels can program some tissues to burn more energy.”
Botezelli, J.D., Overby, P., Lindo, L. et al. Adipose depot-specific upregulation of Ucp1 or mitochondrial oxidative complex proteins are early consequences of genetic insulin reduction in mice. American Journal of Physiology, Endocrinology and Metabolism [online] 2020 https://doi.org/10.1152/ajpendo.00128.2020
Thanks to CIHR for the funding and to the all the members of the team who participated. The project was lead by a visiting fellow from Brazil, Dr. J Diego Botezelli, and supported my multiple colleagues in the lab.