Dulloo Abdul G
Department of Endocrinology, Metabolism & Cardiovascular System, Faculty of Science & Medicine, University of Fribourg, Chemin du musée 5, Fribourg, 1700, Switzerland.
Rev Endocr Metab Disord. 2025 May 26. doi: 10.1007/s11154-025-09970-9.
Across the spectrum of weight regain, ranging from cachexia rehabilitation and catch-up growth to obesity relapse, the recovery rate of body fat is often disproportionate relative to lean tissue recovery. Such preferential 'catch-up fat' is in part attributed to an increase in metabolic efficiency and embodied in the concept that 'metabolic adaptation' or 'adaptive thermogenesis' in response to large weight deficits can persist during weight regain to accelerate fat stores recovery. This paper reviews the evidence in humans for the existence of this thrifty metabolism driving catch-up fat within the framework of a feedback loop between fat stores depletion and suppressed thermogenesis. The search for its effector mechanisms suggests that whereas adaptive thermogenesis during weight loss results primarily from central suppression of sympathetic nervous system and hypothalamic-pituitary-thyroid axis, its persistence during weight regain for accelerating fat recovery is primarily mediated through peripheral tissue resistance to the actions of this systemic neurohormonal network. Emerging evidence linking it to an upregulation of skeletal muscle type 3 deiodinase (D3), the main thyroid hormone inactivating enzyme, along with slowed muscle metabolism and altered contractile properties, suggest that D3-induced muscle hypothyroidism is a key feature of such peripheral resistance. These findings underlying a role of skeletal muscle hypothyroidism in adaptive thermogenesis driving catch-up fat, but which can also concomitantly compromise muscle functionality, have been integrated into a mechanistic framework to explain how weight cycling and large weight fluctuations across the lifespan can predispose to sarcopenic obesity.
在体重恢复的整个范围内，从恶病质康复、追赶生长到肥胖复发，身体脂肪的恢复率相对于瘦组织的恢复往往不成比例。这种优先的“追赶性脂肪”部分归因于代谢效率的提高，体现在这样的概念中，即响应大幅体重下降而产生的“代谢适应”或“适应性产热”在体重恢复期间可能持续存在，以加速脂肪储存的恢复。本文回顾了人类中存在这种节俭代谢驱动追赶性脂肪的证据，该证据存在于脂肪储存耗竭和产热受抑制之间的反馈回路框架内。对其效应机制的探索表明，虽然体重减轻期间的适应性产热主要源于交感神经系统和下丘脑 - 垂体 - 甲状腺轴的中枢抑制，但其在体重恢复期间持续存在以加速脂肪恢复主要是通过外周组织对这种全身神经激素网络作用的抵抗来介导的。将其与骨骼肌3型脱碘酶（D3）上调相关的新证据，D3是主要的甲状腺激素失活酶，同时伴有肌肉代谢减慢和收缩特性改变，表明D3诱导的肌肉甲状腺功能减退是这种外周抵抗的关键特征。这些发现揭示了骨骼肌甲状腺功能减退在驱动追赶性脂肪的适应性产热中的作用，但这也可能同时损害肌肉功能，已被整合到一个机制框架中，以解释体重循环和一生中的大幅体重波动如何易导致肌少症性肥胖。
