Heshka J T, Jones P J
School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
Life Sci. 2001 Jul 20;69(9):987-1003. doi: 10.1016/s0024-3205(01)01201-2.
Leptin is a hormone believed to control appetite and regulate body weight via receptors in the hypothalamus. Much is known about the structure of the functional, or long, form of the leptin receptor, OB-Rb. However, the mechanism by which the receptor regulates leptin's biological action is unknown. Both the type and amount of dietary fat have been shown to affect factors involved in OB-Rb binding and signaling, as well as the morphology of hypothalamic cell membranes. Thus, the following review article examines possible mechanisms by which dietary fat may affect OB-Rb functioning at the hypothalamic level. Dietary fat can alter the fatty acid make-up of membranes, such as the polyunsaturated:saturated fat ratio, changing membrane fluidity and possibly leading to an enhancement or impairment of the structure and/or function of any membrane-associated receptor complexes. Dietary fat also interferes in biochemical pathways involving leptin, OB-Rb, and other neurons containing neuropeptides under OB-Rb's control, such as neuropeptide Y (NPY), proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Increased monounsaturated fat increases cyclic adenosine monophosphate (cAMP) levels, possibly reducing mitogen-activated protein kinase (MAPK) activation and interrupting leptin signaling through Janus kinase/signal tranducers and activators of transcription (JAK/STAT) pathways. Dietary induced alterations in hypothalamic cell membranes, SNS activity, or other factors involved in OB-Rb function form a possible basis for the control of leptin's effects on body composition and appetite. Improving the biological activity of leptin by diet modification may exist as a practical strategy for the treatment of obesity and related disorders.
瘦素是一种通过下丘脑受体控制食欲并调节体重的激素。人们对功能性或长形式的瘦素受体OB-Rb的结构了解很多。然而，该受体调节瘦素生物学作用的机制尚不清楚。已表明膳食脂肪的类型和量都会影响与OB-Rb结合和信号传导相关的因素，以及下丘脑细胞膜的形态。因此，以下综述文章探讨了膳食脂肪可能在下丘脑水平影响OB-Rb功能的潜在机制。膳食脂肪可改变膜的脂肪酸组成，如多不饱和脂肪酸与饱和脂肪酸的比例，改变膜流动性，并可能导致任何与膜相关的受体复合物的结构和/或功能增强或受损。膳食脂肪还会干扰涉及瘦素、OB-Rb以及受OB-Rb控制的其他含有神经肽的神经元的生化途径，如神经肽Y（NPY）、阿黑皮素原（POMC）和可卡因及苯丙胺调节转录物（CART）。单不饱和脂肪增加会提高环磷酸腺苷（cAMP）水平，可能会减少丝裂原活化蛋白激酶（MAPK）的激活，并通过Janus激酶/信号转导子和转录激活子（JAK/STAT）途径中断瘦素信号传导。膳食诱导的下丘脑细胞膜、交感神经系统（SNS）活性或其他与OB-Rb功能相关的因素的改变，可能构成控制瘦素对身体成分和食欲影响的基础。通过饮食调整提高瘦素的生物活性可能是治疗肥胖及相关疾病的一种实用策略。
