Brain protein OPA1 shown to control fat intake and weight, with sex-specific effects
Researchers found that the mitochondrial protein OPA1 in hypothalamic MC4R neurons regulates dietary fat consumption and body weight, with distinct responses in male and female mice.
A study led by Professor Shigenobu Matsumura at Osaka Metropolitan University identified the mitochondrial fusion protein OPA1 within hypothalamic MC4R neurons as a regulator of fat intake and weight gain. Mice lacking OPA1 in these neurons ate more, accumulated extra weight with age, and became obese, particularly when offered soybean oil. In normal male mice, dietary fat boosted OPA1 expression, a change not observed in females, indicating a sex-dependent mechanism.
When given a choice between standard chow and oil, OPA1-deficient mice, especially females, favored the fatty option and gained additional weight. The MC4R agonist setmelanotide reduced appetite in both control and OPA1-deficient males, but its effect was markedly weaker in OPA1-deficient females. The authors suggest that these neuronal and sex differences could inform more personalized obesity treatments. The results were published in the FASEB Journal.
Why it matters
Understanding how brain proteins control fat cravings may lead to better, sex-specific obesity therapies.
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