Obesity is a growing global health challenge that increases the risk of type 2 diabetes, cardiovascular disease, and other metabolic disorders. While many factors contribute to weight gain, researchers are examining how high-fat foods commonly found in grocery stores influence appetite and body weight. New research suggests that the brain protein optic atrophy type 1 (OPA1) may help explain how dietary fat affects hunger, obesity risk, and responses to weight-loss medication.
Although overeating may appear to begin in the stomach, appetite is primarily regulated by the brain. Scientists are still working to understand how dietary fat communicates with the nervous system, which controls hunger, food intake, energy balance, and body weight.
Brain protein OPA1 may regulate appetite and obesity risk
To explore this connection, a research team led by Professor Shigenobu Matsumura of the Osaka Metropolitan University Graduate School of Life and Ecology studied optic atrophy type 1 (OPA1). This mitochondrial fusion protein is found in hypothalamic MC4R neurons, where it helps maintain mitochondrial function and support energy metabolism.
The researchers compared normal mice with mice in which OPA1 had been specifically deleted from MC4R neurons. To examine how OPA1 influences appetite, dietary fat intake, and weight gain, the mice were given unlimited access to soybean oil as a source of dietary fat.
Dietary fat affects male and female mice differently
The study found that soybean oil increased OPA1 expression in male mice with normal MC4R neurons. However, this increase was not observed in female mice. Mice lacking OPA1 ate more food, gained excess weight as they aged, and eventually developed obesity.
When given a choice between a standard diet and soybean oil, the OPA1-deficient mice consumed more dietary fat and gained more weight. These effects were especially pronounced in female mice, suggesting that OPA1 may contribute to sex-specific differences in appetite regulation and obesity susceptibility.
Response to obesity medication also differs by sex
The researchers also tested setmelanotide, an anti-obesity medication that activates MC4R pathways. The drug successfully reduced appetite in both control and OPA1-deficient male mice. In contrast, female mice lacking OPA1 showed a significantly weaker appetite-suppressing response.
“Our findings provide important insights into the mechanisms underlying obesity from the perspective of neuroenergy metabolism,” said Professor Matsumura. “The observed sex differences in OPA1 response and obesity susceptibility may be useful for developing obesity treatments and future personalized medicine approaches.”
The study results were published in the FASEB Journal.
Source: www.sciencedaily.com