Insulin Resistance in the Brain

Insulin is an important hormone for the regulation of energy: Insulin is released in response to glucose in the blood stream where it facilitates the removal of glucose from the blood. After glucose is removed from the blood, it can be burned for energy or stored as fat. Insulin accomplishes this by communicating with the cells mitochondria, but when cells have an impaired response to these communications we consider them to be insulin resistant.

The major organ which one thinks of when we talk about insulin is the pancreas. However, insulin involves another, very important organ: the brain!

Studies have found the brain’s insulin response plays a crucial role in the regulation of hunger and eating behavior. Not every brain responds equally to insulin; when one has a reduced or absent insulin response, we call this insulin resistance. Insulin resistance is associated with obesity.

“experimental studies in humans suggested that brain insulin affects peripheral lipid metabolism in visceral adipose tissue and liver. More importantly, insulin delivery to the brain improves whole-body insulin sensitivity by suppressing endogenous glucose production and stimulating glucose uptake into peripheral tissues. Research in animals and humans identified the hypothalamus as one crucial region for this process. As brain insulin resistance also impairs the central nervous control over peripheral energy metabolism, it has been hypothesized that this impairment could result in altered substrate distribution with preferential energy accumulation in unfavorable fat depots.” (1)

Weight Loss

When starting a weight loss regiment, patients with higher levels of brain insulin sensitivity achieved a greater reduction in body weight and total adipose tissue. “By contrast, brain insulin-resistant individuals showed a slight weight loss in the first 9 months of the program, and already regained body weight as well as total and visceral adipose tissue during the subsequent months of lifestyle intervention” (1). Patients with higher brain insulin sensitivity also saw the greatest reduction of total dietary intake during the study period.

Body Composition

Hypothalamic insulin sensitivity plays a role in determining body fat distribution. Patients with higher brain insulin sensitivity had less visceral adipose tissue, but there was no association with subcutaneous adipose tissue. Thus, the ratio of visceral to subcutaneous adipose tissue, an important indicator of metabolic health, is correlated to brain insulin sensitivity.

Final Thoughts

These results demonstrate the importance of treating insulin resistance as a part of a successful weight loss program. Addressing insulin resistance will lead to faster weight loss, more favorable body composition, and improved likelihood of keeping the weight off.

(1). Kullmann, S., Valenta, V., Wagner, R. et al. Brain insulin sensitivity is linked to adiposity and body fat distribution. Nat Commun 11, 1841 (2020). Retrieved from: