Ma Xinran, Xu Lingyan, Mueller Elisabetta
Genetic of Development and Disease Branch; National Institute of Diabetes and Digestive and Kidney Disease; National Institutes of Health ; Bethesda, MD, USA.
Adipocyte. 2015 May 7;4(4):325-8. doi: 10.1080/21623945.2015.1028700. eCollection 2015 Oct-Dec.
Obesity and diabetes are major health concerns worldwide. Western diets, often calorically rich, paired with sedentary habits are driving the current worldwide epidemic of pediatric and adult obesity. In addition, age related energy imbalances lead to increased adiposity and metabolic disorders later in life, making the middle aged population particularly susceptible. Here we discuss how Forkhead box A3 (Foxa3), a family member of the forkhead box binding proteins, can potentially contribute to pathology by playing a double role in metabolism. Recent data revealed that Foxa3 favors the selective expansion of visceral depots under high caloric conditions (e.g., high fat diet) and suppresses subcutaneous fat tissue energy expenditure during aging. This evidence suggests that Foxa3 acts to both preserve and conserve calories, by accumulating fat and by reducing metabolic burn. In other words, Foxa3 appears to function to enable energy "hoarding," which may be critical for survival of organisms with intermittent exposure to external caloric sources, but pathologic in circumstances where calories are abundant. Understanding how this "calorie hoarder gene" functions may suggest approaches to combat obesity and associated metabolic disorders.
肥胖和糖尿病是全球主要的健康问题。西方饮食通常热量丰富，再加上久坐不动的习惯，正推动着当前全球范围内儿童和成人肥胖症的流行。此外，与年龄相关的能量失衡会导致晚年肥胖和代谢紊乱加剧，使中年人群尤其易受影响。在此，我们讨论叉头框A3（Foxa3），一种叉头框结合蛋白家族成员，如何通过在新陈代谢中发挥双重作用而可能导致病理变化。最近的数据显示，Foxa3在高热量条件下（如高脂饮食）有利于内脏脂肪库的选择性扩张，并在衰老过程中抑制皮下脂肪组织的能量消耗。这一证据表明，Foxa3通过积累脂肪和减少代谢消耗来起到保存和储存热量的作用。换句话说，Foxa3似乎起到了使能量“囤积”的作用，这对于间歇性接触外部热量来源的生物体的生存可能至关重要，但在热量充足的情况下则是病理性的。了解这种“热量囤积基因”的功能可能会为对抗肥胖及相关代谢紊乱提供方法。
