Might the Brain Not Know the Body is Fat?

A new study published in Cell Metabolism - Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons - found that in an obese state, the brain becomes "unaware" the body is fat. These findings, in an animal model using obese mice, showed that a sensor in the brain, that normally detects a critical fat hormone, fails to engage to keeps energy balance in check. Without that signal, various metabolic pathways fail to blunt appetite and keep calorie consumption under control.

As Scientific American opened their article about the research, "Could fat be in the brain of the beholder? A new study shows that signals in the brain that warn appetite-modulating neurons of excess fat stores can be suppressed, making the brain unaware of the body's condition. The result: the body becomes completely ignorant about its own makeup and thus makes no attempt to increase energy expenditure or reduce appetite to help shave flab."

The biological sensors in question? A suppressor called SOCS-3, is believed responsible for contributing to a loss of sensitivity to the hormone leptin. The researchers found "leptin binds to a receptor in the arcuate nucleus, triggering a cascade of chemical signals that culminate in the activation of SOCS-3, a suppressor that stops the reaction. The scientists determined that obese animals had an adequate quantity of leptin receptors, but that the quantity of SOCS-3 had risen, likely thwarting any activation of the fat hormone."

Why this may be critically important in our understanding of obesity is that those who are obese often have higher circulating levels of leptin, suggesting something else is limiting it's action. In this animal model it was found that mice consuming identical calorie intakes did not all maintain similar weight - some became obese. After tweaking the macronutrients (in this instance reducing fat since the mice used in this study are bred to grow obese on a high-fat diet) while maintaining the calorie intake, the mice lost weight back to normal - and, the brain control centers regained sensitivity to leptin.

The researchers caution that the study does not necessarily extrapolate well to humans - additional studies are needed since mice overall have a different physiology than humans. But, the study does have value in the scheme of human metabolism and I hope researchers will continue to look at these metabolic pathways and hormones involved in energy regulation in humans.