Ramírez Sara, Claret Marc
Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain.
FEBS Lett. 2015 Jun 22;589(14):1678-87. doi: 10.1016/j.febslet.2015.04.025. Epub 2015 Apr 23.
The prevalence of obesity has increased worldwide at an alarming rate. However, non-invasive pharmacological treatments remain elusive. Leptin resistance is a general feature of obesity, thus strategies aimed at enhancing the sensitivity to this hormone may constitute an excellent therapeutical approach to counteract current obesity epidemics. Nevertheless, the etiology and neuronal basis of leptin resistance remains an enigma. A recent hypothesis gaining substantial experimental support is that hypothalamic endoplasmic reticulum (ER) stress plays a causal role in the development of leptin resistance and obesity. The objective of this review article is to provide an updated view on current evidence connecting hypothalamic ER stress with leptin resistance. We discuss the experimental findings supporting this hypothesis, as well as the potential causes and underlying mechanisms leading to this metabolic disorder. Understanding these mechanisms may provide key insights into the development of novel intervention approaches.
肥胖的患病率在全球范围内以惊人的速度上升。然而，非侵入性药物治疗仍然难以实现。瘦素抵抗是肥胖的一个普遍特征，因此旨在增强对这种激素敏感性的策略可能构成对抗当前肥胖流行的一种极佳治疗方法。尽管如此，瘦素抵抗的病因和神经基础仍然是一个谜。最近一个获得大量实验支持的假说是，下丘脑内质网（ER）应激在瘦素抵抗和肥胖的发展中起因果作用。这篇综述文章的目的是提供关于下丘脑ER应激与瘦素抵抗之间现有证据的最新观点。我们讨论了支持这一假说的实验结果，以及导致这种代谢紊乱的潜在原因和潜在机制。了解这些机制可能为开发新的干预方法提供关键见解。
