Milhem Fadia, Komarnytsky Slavko
Plants for Human Health Institute, NC State University, 600 Laureate Way, Kannapolis, NC 28081, USA.
Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, NC 27695, USA.
Metabolites. 2023 Sep 15;13(9):1016. doi: 10.3390/metabo13091016.
Obesity is a multifactorial disorder that is remarkably heterogeneous. It presents itself in a variety of phenotypes that can be metabolically unhealthy or healthy, associate with no or multiple metabolic risk factors, gain extreme body weight (super-responders), as well as resist obesity despite the obesogenic environment (non-responders). Progression to obesity is ultimately linked to the overall net energy balance and activity of different metabolic fluxes. This is particularly evident from variations in fatty acids oxidation, metabolic fluxes through the pyruvate-phosphoenolpyruvate-oxaloacetate node, and extracellular accumulation of Krebs cycle metabolites, such as citrate. Patterns of fat accumulation with a focus on visceral and ectopic adipose tissue, microbiome composition, and the immune status of the gastrointestinal tract have emerged as the most promising targets that allow personalization of obesity and warrant further investigations into the critical issue of a wider and long-term weight control. Advances in understanding the biochemistry mechanisms underlying the heterogenous obesity phenotypes are critical to the development of targeted strategies to maintain healthy weight.
肥胖是一种多因素疾病，具有显著的异质性。它以多种表型出现，这些表型在代谢上可能不健康或健康，与无或多种代谢风险因素相关，体重极度增加（超级反应者），以及尽管处于致肥胖环境中仍抵抗肥胖（无反应者）。肥胖的进展最终与总体净能量平衡和不同代谢通量的活动有关。这在脂肪酸氧化、通过丙酮酸 - 磷酸烯醇丙酮酸 - 草酰乙酸节点的代谢通量以及柠檬酸等三羧酸循环代谢物的细胞外积累的变化中尤为明显。以内脏和异位脂肪组织、微生物群组成以及胃肠道免疫状态为重点的脂肪积累模式已成为最有前景的靶点，这些靶点有助于肥胖的个性化，并为更广泛和长期的体重控制这一关键问题提供进一步研究的依据。了解异质性肥胖表型背后的生物化学机制的进展对于制定维持健康体重的靶向策略至关重要。
