The past 50 years of interdisciplinary research in humans and model organisms has delivered unprecedented insights into the mechanisms through which diet affects energy balance. However, translating these results to prevent and treat obesity and its associated diseases remains challenging. Given the vast scope of this literature, we focus this Review on recent conceptual advances in molecular nutrition targeting the management of energy balance, including emerging dietary and pharmaceutical interventions and their interactions with the human gut microbiome. Notably, multiple current dietary patterns of interest embrace moderate-to-high fat intake or prioritize the timing of eating over macronutrient intake. Furthermore, the rapid expansion of microbiome research findings has complicated multiple longstanding tenets of nutrition while also providing new opportunities for intervention. Continued progress promises more precise and reliable dietary recommendations that leverage our growing knowledge of the microbiome, the changing landscape of clinical interventions, and our molecular understanding of human biology.

过去 50 年对人类和模式生物的跨学科研究对饮食影响能量平衡的机制提供了前所未有的见解。然而，将这些结果转化为预防和治疗肥胖及其相关疾病仍然具有挑战性。鉴于该文献范围广泛，我们将这篇综述重点关注以能量平衡管理为目标的分子营养学的最新概念进展，包括新兴的饮食和药物干预措施及其与人类肠道微生物组的相互作用。值得注意的是，当前多种令人感兴趣的饮食模式包括中度至高脂肪摄入量或优先考虑进食时间而不是大量营养素摄入。此外，微生物组研究结果的迅速扩展使多种长期存在的营养原则变得复杂，同时也提供了新的干预机会。持续的进展有望提供更精确、更可靠的饮食建议，这些建议利用了我们对微生物组不断增长的知识、不断变化的临床干预措施以及我们对人类生物学的分子理解。