A protein in brain cells involved in appetite may help influence how much dietary fat animals eat and how their body weight changes over time, according to new research in mice.
Researchers found that mice missing the protein in a specific group of appetite-regulating brain cells ate more food and gained more weight as they aged. When the animals were later given a choice between their usual food and an additional source of dietary fat, mice without the protein also consumed more fat. The study, published in The FASEB Journal, offers an early look at one of the biological systems that may help the brain regulate eating and body weight.
Appetite is controlled by a complex system of signals between the brain and the rest of the body. Researchers have long studied certain brain cells involved in hunger, energy use and body weight.
The new study focused on a protein called OPA1 that helps those cells function normally.
Researchers created mice that lacked OPA1 in a group of appetite-regulating brain cells, then compared their eating behavior and weight with mice that still produced the protein.
The mice without OPA1 ate more and gradually gained more weight, eventually developing obesity.
Researchers then gave the animals access to both their usual food and soybean oil as an additional source of dietary fat. Mice without OPA1 consumed more of the oil and gained more weight than the comparison mice.
Soybean oil was the dietary fat researchers chose for this part of the experiment. The study was not designed to test the health effects of soybean oil itself, and the findings do not show that soybean oil interferes with appetite control or is uniquely likely to cause weight gain.
Instead, researchers were using it to test whether changing this brain pathway affected how much fat the mice chose to consume.
The study also found differences between male and female mice.
Soybean oil consumption increased OPA1 levels in the targeted brain cells of male mice, but researchers did not see the same response in females. Female mice without OPA1 also showed particularly large increases in fat intake and weight.
Researchers explored those differences further using setmelanotide, a medication that acts on the same appetite-regulating system.
The drug reduced food intake in male mice whether or not they had normal OPA1 function. In female mice without OPA1, however, the appetite-suppressing effect was weaker.
“Our findings provide key insights into the mechanisms underlying obesity from the perspective of neuronal energy metabolism,” said senior researcher Shigenobu Matsumura, Ph.D., of Osaka Metropolitan University. “The sex differences observed in OPA1 responses and obesity susceptibility may help inform the development of obesity treatments that take them into account, as well as future personalized medicine approaches.”
The findings do not mean females are generally more affected by dietary fat or that men and women will respond differently to particular foods or obesity treatments.
The experiments were conducted in genetically altered mice, and researchers do not yet know whether OPA1 plays the same role in human eating behavior. Appetite and body weight in people are influenced by many biological, psychological, social and environmental factors that cannot be captured in an animal experiment.
The study also did not measure cravings in the way people experience them. The mice voluntarily consumed more dietary fat after the brain protein was disrupted, but that does not necessarily mean they were experiencing anything comparable to a human food craving.
The study was supported by the Public Foundation of Tojuro Iijima Foundation for Food Science and Technology and JSPS KAKENHI, a Japanese government research grant program.