Page Laura, McCain Elizabeth, Freemark Michael
Division of Pediatric Endocrinology, Duke University Medical Center, 3000 Erwin Road, Durham, NC 27005, USA.
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27705, USA.
Nutrients. 2025 Sep 4;17(17):2864. doi: 10.3390/nu17172864.
Malnutrition afflicts millions of the world's children and predisposes to death from diarrhea and infectious diseases. Children with severe acute malnutrition (SAM) are at highest risk. Our review of the endocrinology and metabolomics of SAM implicates critical roles for white adipose tissue and its regulatory hormones and growth factors in the adaptation to nutritional deprivation and the restoration of metabolic homeostasis: white adipose provides substrates and energy for hepatic glucose production and cardiopulmonary and central nervous system function, and products of fat metabolism inhibit muscle glucose uptake and utilization and spare muscle protein. Collectively, these effects maintain glucose availability for the brain, red blood cells, and renal medulla and conserve muscle mass. White adipose tissue also secretes leptin, which facilitates the immune response and may protect against mortality from infection. Euglycemia and survival in SAM are thereby prioritized over linear growth, which is suppressed owing to inhibition of insulin-like growth factor 1 production and action. Diversion of energy from growth serves to maintain essential bodily functions in critically ill malnourished children, who have limited energy reserves. Thus, short-term reductions in growth rate have adaptive benefits in SAM. Under favorable conditions, clinical and metabolic recovery are accompanied by catch-up growth, which can mitigate, and in many cases reverse, the stunting of growth in childhood. Nevertheless, clinical recovery can be complicated by preferential accrual of central fat and a relative deficiency of lean/skeletal mass, with potential long-term complications including insulin resistance, glucose intolerance, and metabolic syndrome.
营养不良折磨着全球数百万儿童，使他们易死于腹泻和传染病。患有重度急性营养不良（SAM）的儿童风险最高。我们对SAM的内分泌学和代谢组学的综述表明，白色脂肪组织及其调节激素和生长因子在适应营养剥夺和恢复代谢稳态中起着关键作用：白色脂肪为肝脏葡萄糖生成以及心肺和中枢神经系统功能提供底物和能量，脂肪代谢产物抑制肌肉对葡萄糖的摄取和利用，并节省肌肉蛋白质。总体而言，这些作用维持了大脑、红细胞和肾髓质的葡萄糖供应，并保留了肌肉质量。白色脂肪组织还分泌瘦素，瘦素可促进免疫反应，并可能预防感染导致的死亡。因此，在SAM中，维持血糖正常和生存比线性生长更重要，线性生长因胰岛素样生长因子1的产生和作用受到抑制而被抑制。对于能量储备有限的重症营养不良儿童，将能量从生长中转移出来有助于维持身体的基本功能。因此，短期内生长速度的降低在SAM中有适应性益处。在有利条件下，临床和代谢恢复伴随着追赶生长，这可以减轻并在许多情况下逆转儿童期生长发育迟缓的情况。然而，临床恢复可能会因中心脂肪的优先积累和瘦/骨骼质量的相对不足而变得复杂，潜在的长期并发症包括胰岛素抵抗、葡萄糖不耐受和代谢综合征。
