Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA, USA; Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA.
Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, Cologne, Germany; Max Planck Institute for Biology of Ageing, Cologne, Germany and Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) Cologne, Germany; Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Cell Metab. 2017 Jul 5;26(1):198-211.e5. doi: 10.1016/j.cmet.2017.06.015.
Olfactory inputs help coordinate food appreciation and selection, but their role in systemic physiology and energy balance is poorly understood. Here we demonstrate that mice upon conditional ablation of mature olfactory sensory neurons (OSNs) are resistant to diet-induced obesity accompanied by increased thermogenesis in brown and inguinal fat depots. Acute loss of smell perception after obesity onset not only abrogated further weight gain but also improved fat mass and insulin resistance. Reduced olfactory input stimulates sympathetic nerve activity, resulting in activation of β-adrenergic receptors on white and brown adipocytes to promote lipolysis. Conversely, conditional ablation of the IGF1 receptor in OSNs enhances olfactory performance in mice and leads to increased adiposity and insulin resistance. These findings unravel a new bidirectional function for the olfactory system in controlling energy homeostasis in response to sensory and hormonal signals.
嗅觉输入有助于协调食物的感知和选择，但它们在全身生理学和能量平衡中的作用还知之甚少。在这里，我们证明，条件性敲除成熟嗅觉感觉神经元 (OSN) 的小鼠对饮食诱导的肥胖具有抗性，伴随着棕色和腹股沟脂肪组织中产热的增加。肥胖发生后嗅觉感知的急性丧失不仅阻止了进一步的体重增加，而且还改善了脂肪量和胰岛素抵抗。嗅觉输入的减少刺激交感神经活动，导致白色和棕色脂肪细胞上的β-肾上腺素能受体激活，促进脂肪分解。相反，OSN 中 IGF1 受体的条件性缺失增强了小鼠的嗅觉表现，导致脂肪量增加和胰岛素抵抗。这些发现揭示了嗅觉系统在响应感觉和激素信号控制能量平衡方面的新的双向功能。
