Food & Nutrition Program, Environment & Life Sciences Research Center, Kuwait Institute for Scientific Research, P.O. Box 24885, 13109, Kuwait City, Kuwait.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Neural Dev. 2018 Aug 13;13(1):18. doi: 10.1186/s13064-018-0116-7.
In an earlier study, we identified two neuronal populations, c673a and Fru-GAL4, that regulate fat storage in fruit flies. Both populations partially overlap with a structure in the insect brain known as the mushroom body (MB), which plays a critical role in memory formation. This overlap prompted us to examine whether the MB is also involved in fat storage homeostasis.
Using a variety of transgenic agents, we selectively manipulated the neural activity of different portions of the MB and associated neurons to decipher their roles in fat storage regulation.
Our data show that silencing of MB neurons that project into the α'β' lobes decreases de novo fatty acid synthesis and causes leanness, while sustained hyperactivation of the same neurons causes overfeeding and produces obesity. The α'β' neurons oppose and dominate the fat regulating functions of the c673a and Fru-GAL4 neurons. We also show that MB neurons that project into the γ lobe also regulate fat storage, probably because they are a subset of the Fru neurons. We were able to identify input and output neurons whose activity affects fat storage, feeding, and metabolism. The activity of cholinergic output neurons that innervating the β'2 compartment (MBON-β'2mp and MBON-γ5β'2a) regulates food consumption, while glutamatergic output neurons innervating α' compartments (MBON-γ2α'1 and MBON-α'2) control fat metabolism.
We identified a new fat storage regulating center, the α'β' lobes of the MB. We also delineated the neuronal circuits involved in the actions of the α'β' lobes, and showed that food intake and fat metabolism are controlled by separate sets of postsynaptic neurons that are segregated into different output pathways.
在早期的一项研究中，我们鉴定了两个神经元群体，c673a 和 Fru-GAL4，它们调节果蝇的脂肪储存。这两个群体与昆虫大脑中的一个结构（蘑菇体，MB）部分重叠，MB 在记忆形成中起着关键作用。这种重叠促使我们研究 MB 是否也参与脂肪储存稳态的调节。
使用各种转基因制剂，我们选择性地操纵 MB 的不同部分及其相关神经元的神经活动，以解析它们在脂肪储存调节中的作用。
我们的数据表明，沉默投射到α'β'叶的 MB 神经元会减少新脂肪酸的合成并导致消瘦，而持续过度激活相同的神经元会导致过度进食并导致肥胖。α'β'神经元拮抗并主导 c673a 和 Fru-GAL4 神经元的脂肪调节功能。我们还表明，投射到γ叶的 MB 神经元也调节脂肪储存，可能是因为它们是 Fru 神经元的一个子集。我们能够鉴定出影响脂肪储存、摄食和代谢的神经元的活动。支配β'2 隔室（MBON-β'2mp 和 MBON-γ5β'2a）的胆碱能输出神经元的活动调节食物消耗，而支配α'隔室（MBON-γ2α'1 和 MBON-α'2）的谷氨酸能输出神经元控制脂肪代谢。
我们鉴定出一个新的脂肪储存调节中心，即 MB 的α'β'叶。我们还描绘了涉及α'β'叶作用的神经元回路，并表明食物摄入和脂肪代谢是由不同的突触后神经元控制的，这些神经元被分离到不同的输出通路中。
