Mauvais-Jarvis Franck, Arnold Arthur P, Reue Karen
Diabetes Discovery & Gender Medicine Laboratory, Section of Endocrinology & Metabolism, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Department of Integrative Biology & Physiology, University of California, Los Angeles, CA 90095, USA.
Cell Metab. 2017 Jun 6;25(6):1216-1230. doi: 10.1016/j.cmet.2017.04.033.
In animal models, the physiological systems involved in metabolic homeostasis exhibit a sex difference. Investigators often use male rodents because they show metabolic disease better than females. Thus, females are not used precisely because of an acknowledged sex difference that represents an opportunity to understand novel factors reducing metabolic disease more in one sex than the other. The National Institutes of Health (NIH) mandate to consider sex as a biological variable in preclinical research places new demands on investigators and peer reviewers who often lack expertise in model systems and experimental paradigms used in the study of sex differences. This Perspective discusses experimental design and interpretation in studies addressing the mechanisms of sex differences in metabolic homeostasis and disease, using animal models and cells. We also highlight current limitations in research tools and attitudes that threaten to delay progress in studies of sex differences in basic animal research.
在动物模型中,参与代谢稳态的生理系统存在性别差异。研究人员通常使用雄性啮齿动物,因为它们比雌性更易表现出代谢疾病。因此,雌性动物不被使用恰恰是因为存在公认的性别差异,而这种差异为了解在一种性别中比另一种性别更能减少代谢疾病的新因素提供了契机。美国国立卫生研究院(NIH)要求在临床前研究中将性别视为生物学变量,这对研究人员和同行评审人员提出了新的要求,他们往往缺乏性别差异研究中所使用的模型系统和实验范式方面的专业知识。本观点文章讨论了使用动物模型和细胞来研究代谢稳态和疾病中性别差异机制的实验设计与解读。我们还强调了研究工具和态度方面当前存在的局限性,这些局限性可能会阻碍基础动物研究中性别差异研究的进展。