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This study used a validated mass spectrometry method to measure oxytocin levels in mouse blood plasma across different life stages, sexes, and in diet-induced obesity. Plasma oxytocin increased with age in both male and female mice but did not differ between sexes, while hypothalamic oxytocin expression generally mirrored these patterns. In obesity models, female mice showed greater resistance to weight gain and maintained higher oxytocin levels compared to males, suggesting sex-specific oxytocin regulation in metabolic control.
Why it matters
These findings help clarify contradictory data about oxytocin measurement and suggest the hormone plays a sex-dependent role in obesity and metabolism. The validated measurement technique could improve future oxytocin research, and the sex differences observed may inform development of targeted obesity treatments.
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⚠️ Preprint – Noch nicht peer-reviewed
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Objective: Oxytocin (Oxt) assessment in plasma is challenging, and available data are contradictory. We aimed to assess circulating Oxt in mice by a validated nano-liquid chromatography/mass-spectrometry (nLC-MS/MS) protocol, combined with Oxt hypothalamic expression in different sex, life stages, and in diet-induced obesity. Methods: We assessed plasma Oxt by nLC-MS/MS, Oxt hypothalamic expression by qPCR, and Oxt-immunoreactive neuron and fiber densities by immunohistochemistry and morphometric analyses in C57BL/6 mice at 21 and 60 days of life (p21 and p60, respectively). Mice in normo-fed condition and following 12 weeks of high-fat diet (HFD) were studied alongside food intake and hypothalamic expression of its regulators. Results: Circulating Oxt does not vary based on sex at p21 and p60 but increases with aging. While hypothalamic Oxt mRNA expression followed the same trend across both sexes, Oxt neuron and fiber densities exhibited a similar trend only in females. Plasma vasopressin (Avp) followed Oxt trend in females but was opposite in males and was not mirrored by Avp mRNA hypothalamic expression. HFD-fed females were more resistant to weight gain compared to males and displayed higher Oxt plasma levels and hypothalamic expression. Sex dimorphism in food intake and hypothalamic expression of Avp and of key anorexigenic and orexigenic neuropeptides was detected. Conclusions: Oxt plasma levels are higher in adulthood compared to weaning in mice of both sexes who displayed similar concentrations. Oxt plasma levels are mirrored by Oxt hypothalamic expression. In obesity, females display a lower increase in body weight but higher Oxt plasma levels than males.
Source: Plasma oxytocin measured by LC-MS/MS varies with life stage, sex, and obesity in mice