Association between Weight Gain and Sex-Related Differences through 5-Fluorouracil Administration.

Area of Science:

• Oncology
• Endocrinology
• Neuroscience

Background:

• Sex differences in cancer incidence, survival, and drug efficacy are increasingly recognized.
• Weight gain is a reported side effect in female breast cancer patients undergoing specific chemotherapy regimens like CMF.
• Mechanisms underlying these sex-specific chemotherapy effects require further investigation.

Purpose of the Study:

• To investigate the role of 5-fluorouracil (5-FU) in causing weight gain.
• To explore sex-related differences in response to 5-FU administration.
• To elucidate the underlying biological mechanisms of 5-FU-induced weight gain in female mice.

Main Methods:

• Experiments were conducted using mice to assess weight changes and food intake following 5-FU administration.
• Analysis included measuring norepinephrine, adrenergic receptor expression (α1 and α2), estradiol, and ghrelin levels in female mice.

Main Results:

• 5-FU administration led to significant weight gain and increased food intake in female mice compared to controls.
• Female mice showed elevated norepinephrine and α1/α2-adrenergic receptor expression.
• Reduced estradiol and increased ghrelin levels were observed in female mice treated with 5-FU.

Conclusions:

• 5-FU administration induces sex differences in weight gain, primarily affecting female mice.
• Increased food intake, driven by elevated norepinephrine, adrenergic receptors, and ghrelin, alongside reduced estradiol, contributes to 5-FU-induced weight gain in females.
• These findings provide mechanistic insights into chemotherapy-related weight gain in female breast cancer patients.