Katarina T Borer, School of Kinesiology, The University of Michigan, Ann Arbor, MI 48109, United States.
World J Diabetes. 2014 Oct 15;5(5):606-29. doi: 10.4239/wjd.v5.i5.606.
A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses.
重新审视控制进食、运动和代谢的机制，促使我们提出一个新的解释模型，该模型包含五个特征：（1）自主神经系统（ANS）；（2）下丘脑视交叉上核（SCN）主钟，在昼夜节律框架内平衡副交感消化和吸收功能以及交感运动和产热能量消耗；（3）ANS/SCN 命令与犒赏脑基质的相互作用，包括多巴胺能投射到腹侧纹状体和边缘以及皮质前脑。这些与循环 ghrelin 和通过黑色素浓缩激素和食欲素-下丘脑肽信号传递的外侧下丘脑神经元相互作用，驱动非稳态进食和运动动机行为；（4）来自胃和脂肪组织的瘦素对胰岛素的反向调节：通过瘦素增强胆囊收缩素介导的饱腹感、抑制胰岛素分泌、瘦素脂肪分解抑制胰岛素的脂肪生成、以及调节外周组织和大脑对胰岛素作用的敏感性。因此，体重减轻引起的瘦素减少会提高胰岛素敏感性，并促进其副交感神经合成代谢作用，而肥胖引起的瘦素增加会抑制胰岛素的脂肪生成作用；（5）瘦素抑制骨矿物质积累，表明瘦素可能有助于维持骨骼、瘦体组织以及脂肪组织质量的稳定性。
