Obesity causes low testosterone in men, which affects muscle mass and cognition, as well as reproductive function by reducing sperm counts and decreasing libido.
Although scientists know this, the way obesity produces these changes, in addition to causing cardiovascular disease and type 2 diabetes, is not fully understood.
Using mice fed a high-fat diet to mimic human obesity, a research team led by the University of California, Riverside, found that obesity causes chronic changes in the brain.
The team found that the mice's brains showed reduced communication between neurons and decreased regulation of receptors that normally tell the brain when there is enough energy and to stop eating.
"This may explain why we can't stop eating too many calories," said Djordica Kos, professor of biomedical sciences at the School of Medicine, who led the study. "Overweight mice also had lower testosterone in their blood and lower sperm counts."
Koss explained that reproductive function is regulated by the hypothalamic-pituitary-gonadal axis, a feedback loop that regulates reproduction and sexual development.
The hypothalamus is a complex region of the brain that regulates food intake, temperature, thirst, and reproduction. It contains nerve cells that regulate the synthesis and release of hormones from the pituitary gland at the base of the brain, which then regulate the synthesis of testosterone and sperm production in the testicles in males (and the production of estrogen and ovulation in females).
“When these neurons in the hypothalamus don’t function properly, as in obesity, it causes lower levels of pituitary hormone and decreased production of testosterone and sperm,” Koss explained. “Surprisingly, we found that the main site of obesity’s effects is the brain, not the testes or the pituitary gland, disrupting the normal functioning of neurons that regulate reproduction.”
Koss stressed that the same brain mechanisms that her lab discovered in mice for the study exist in humans. “We have the same neurons that regulate reproduction and food intake, and the same hormones in the pituitary gland that regulate testicular function in men, such as testosterone synthesis and sperm production,” she said.
Koss explained that neurons in the brain are connected and communicate with each other via synapses. Neurons that regulate food intake and energy expenditure interact with neurons that regulate reproduction to coordinate their functions, because reproduction requires energy.
“Growing a child requires a lot of energy,” she continued. “We counted the number of synapses in neurons that regulate reproduction in the brain and identified fewer synaptic connections in mice fed a high-fat diet. We still don’t know exactly how this happens, but now that we have identified the specific neurons and synaptic molecules that are affected by obesity, we can focus our future studies on trying to understand these observations.”