Metabolic homeostasis operates differently in men and women. This sex asymmetry is the result of evolutionary adaptations that enable women to resist loss of energy stores and protein mass while remaining fertile in times of energy deficit. During starvation or prolonged exercise, women rely on oxidation of lipids, which are a more efficient energy source than carbohydrates, to preserve glucose for neuronal and placental function and spare proteins necessary for organ function. Carbohydrate reliance in men could be an evolutionary adaptation related to defence and hunting, as glucose, unlike lipids, can be used as a fuel for anaerobic high-exertion muscle activity. The larger subcutaneous adipose tissue depots in healthy women than in healthy men provide a mechanism for lipid storage. As female mitochondria have higher functional capacity and greater resistance to oxidative damage than male mitochondria, uniparental inheritance of female mitochondria may reduce the transmission of metabolic disorders. However, in women, starvation resistance and propensity to obesity have evolved in tandem, and the current prevalence of obesity is greater in women than in men. The combination of genetic sex, programming by developmental testosterone in males, and pubertal sex hormones defines sex-specific biological systems in adults that produce phenotypic sex differences in energy homeostasis, metabolic disease and drug responses.

男性和女性的代谢稳态运作方式不同。这种性别不对称是进化适应的结果，进化适应使女性能够抵抗能量储存和蛋白质质量的损失，同时在能量不足时保持生育能力。在饥饿或长时间运动期间，女性依靠脂质的氧化（比碳水化合物更有效的能量来源）来保存神经元和胎盘功能所需的葡萄糖，并保留器官功能所需的蛋白质。男性对碳水化合物的依赖可能是一种与防御和狩猎相关的进化适应，因为与脂质不同，葡萄糖可以用作无氧高强度肌肉活动的燃料。健康女性的皮下脂肪组织库比健康男性更大，这提供了脂质储存的机制。由于雌性线粒体比雄性线粒体具有更高的功能能力和更强的抗氧化损伤能力，因此雌性线粒体的单亲遗传可能会减少代谢紊乱的传播。然而，在女性中，饥饿抵抗力和肥胖倾向是同步进化的，目前女性肥胖患病率高于男性。遗传性别、男性发育睾酮的编程以及青春期性激素的结合定义了成人的性别特异性生物系统，该系统在能量稳态、代谢疾病和药物反应方面产生表型性别差异。