The researchers found that the growth hormone can act in a way that hinders weight loss. They already knew that growth hormone receptors, which can be found in large quantities in the muscle, liver, tissue, and other organs, directly play a role in growth metabolism. However, in their recent study, they found that brains are also full of growth hormone receptors and that they are involved in metabolic responses that conserve energy when you are hungry or on a diet.
“This discovery has important implications in terms of understanding why it’s so hard to lose weight,” explained Jose Donato Junior, a professor at USP and one of the researchers of the study.
Specifically, the researchers found that in response to weight loss, growth hormone acts on the brain by increasing its levels. They discovered that growth hormone receptors in the hypothalamus, the highest center of the autonomic nervous system, activate a small population of neurons called agouti-related protein (AgRP). These neurons, in turn, increase the production of AgRP, which increase appetite and reduces energy metabolism and expenditure.
“AgRP is one of the most powerful appetite stimulants. It's curious to see how a small number of AgRP neurons, only a few thousand out of the billions of neurons in the hypothalamus, can play such an important role,” Donato said.
For the study, the researchers looked at the influence of growth hormone signaling on AgRP neurons in mice with AgRP-specific growth hormone receptor ablation or AgRP GHR knockout (AgRP GHR KO) mice and a control group comprising wild-type mice.
In different experiments, they measured the animals’ whole-body expenditure when subjected to a diet with a 60-percent food restriction. They wanted to find out whether a lack of adaptive response to the resulting energy decline would greatly affect energy balance.
Their results showed that the control mice reduced energy expenditure during food restriction, which is consistent with the adaptive responses that save energy in this state. In AgRP GHR KO mice, their energy expenditure decreased significantly less. This suggested that they failed to save energy as efficiently as the control mice.
Because of this, the AgRP GHR KO mice showed a higher rate of weight loss, mostly because of decreased fat mass or energy reserves, as well as the loss of lean mass in vital organs, bone, muscle, ligaments, tendons, and body fluids.
“In other words, we discovered that weight loss triggers an increase in hypothalamus GH levels, which activates the AgRP neurons, making weight loss harder and intensifying the sense of hunger. That's precisely the same function leptin performs,” Donato said.
Donato further explained that humans have two energy conservation mechanisms – one activated by leptin and the other by the growth hormone. One functions as a backup for the other. For this reason, weight loss treatments solely based on leptin are ineffective. The growth hormone mechanism must be dealt with simultaneously. Therefore, when coming up with a weight loss plan, growth hormone levels also need to be considered.
The team published their findings in the journal Nature Communications.