Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofisica, Sao Paulo 05508-000, Brazil.
Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofisica, Sao Paulo 05508-000, Brazil..
Life Sci. 2022 Jul 15;301:120636. doi: 10.1016/j.lfs.2022.120636. Epub 2022 May 12.
The present study aims to compare the responses between male and female C57BL/6 mice to multiple metabolic challenges to understand the importance of sex in the control of energy homeostasis.
Male and female C57BL/6 mice were subjected to nutritional and hormonal challenges, such as food restriction and refeeding, diet-induced obesity, feeding response to ghrelin and leptin, ghrelin-induced growth hormone secretion, and central responsiveness to ghrelin and leptin. The hypothalamic expression of transcripts that control energy homeostasis was also evaluated.
Male mice lost more weight and lean body mass in response to food restriction, compared to females. During refeeding, males accumulated more body fat and exhibited lower energy expenditure and glycemia, as compared to females. Additionally, female mice exhibited a higher protection against diet-induced obesity and related metabolic imbalances in comparison to males. Low dose ghrelin injection elicited higher food intake and growth hormone secretion in male mice, whereas the acute anorexigenic effect of leptin was more robust in females. However, the sex differences in the feeding responses to ghrelin and leptin were not explained by variations in the central responsiveness to these hormones nor by differences in the fiber density from arcuate nucleus neurons. Female, but not male, mice exhibited compensatory increases in hypothalamic Pomc mRNA levels in response to diet-induced obesity.
Our findings revealed several sexually differentiated responses to metabolic challenges in C57BL/6 mice, highlighting the importance of taking into account sex differences in metabolic studies.
本研究旨在比较雄性和雌性 C57BL/6 小鼠对多种代谢挑战的反应，以了解性别在能量平衡控制中的重要性。
雄性和雌性 C57BL/6 小鼠接受了营养和激素挑战，如食物限制和再喂养、饮食诱导肥胖、对胃饥饿素和瘦素的进食反应、胃饥饿素诱导的生长激素分泌以及对胃饥饿素和瘦素的中枢反应。还评估了控制能量平衡的转录本在下丘脑的表达。
与雌性相比，雄性在食物限制时体重和瘦体重减轻更多。在再喂养期间，与雌性相比，雄性积累更多的体脂肪，表现出较低的能量消耗和血糖。此外，与雄性相比，雌性对饮食诱导的肥胖和相关代谢失衡表现出更高的保护作用。低剂量胃饥饿素注射会引起雄性小鼠更高的食物摄入和生长激素分泌，而瘦素的急性厌食作用在雌性中更为明显。然而，雄性和雌性对胃饥饿素和瘦素的进食反应的性别差异不能用这些激素的中枢反应的变化或弓状核神经元的纤维密度的差异来解释。雌性而不是雄性小鼠在饮食诱导肥胖时表现出下丘脑 Pomc mRNA 水平的代偿性增加。
我们的发现揭示了 C57BL/6 小鼠对代谢挑战的几种性别差异反应，强调了在代谢研究中考虑性别差异的重要性。
