López Miguel, Vidal-Puig Antonio
Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):483-90. doi: 10.1097/MCO.0b013e328302f3d8.
To revise current available information related to the role of brain lipogenic pathways in the regulation of energy homeostasis.
The 'classical' hypothalamic neuropeptide view of feeding regulation has been extensively reviewed and revised during the past few years. Accumulating evidence indicates that the modulation of lipogenesis de novo in the hypothalamus, through selective pharmacologic and genetic manipulation of acetyl-CoA carboxylase, AMP-activated protein kinase, carnitine palmitoyltransferase 1, fatty acid synthase and malonyl-CoA decarboxylase enzymes, has a severe impact on food intake and body weight homeostasis. Furthermore, as these manipulations alter the hypothalamic pool of lipids, such as malonyl-CoA or long chain fatty acyl-CoA or both, the concept of lipids as signals of nutrient abundance able to modulate feeding in the hypothalamus has recently re-emerged.
In this review, we summarize what is known about brain lipogenesis and energy balance and propose further avenues of research. Defining these novel mechanisms could offer new targets for the treatment of obesity and metabolic syndrome.
修订目前有关脑内脂肪生成途径在能量稳态调节中作用的现有信息。
过去几年里,对进食调节的“经典”下丘脑神经肽观点进行了广泛综述和修订。越来越多的证据表明,通过对乙酰辅酶A羧化酶、AMP激活的蛋白激酶、肉碱棕榈酰转移酶1、脂肪酸合酶和丙二酰辅酶A脱羧酶进行选择性药理和基因操作,从而对下丘脑从头脂肪生成进行调节,会对食物摄入和体重稳态产生严重影响。此外,由于这些操作改变了下丘脑脂质池,如丙二酰辅酶A或长链脂肪酰辅酶A或两者,脂质作为营养丰富信号能够调节下丘脑进食的概念最近又重新出现。
在本综述中,我们总结了关于脑内脂肪生成和能量平衡的已知信息,并提出了进一步的研究途径。明确这些新机制可为肥胖和代谢综合征的治疗提供新靶点。