Nath Dharmendra Kumar, Dhakal Subash, Lee Youngseok
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, Republic of Korea.
Elife. 2025 Apr 17;13:RP99258. doi: 10.7554/eLife.99258.
Understanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Previously, we demonstrated the role of TRPγ in nutrient-sensing behavior (Dhakal et al., 2022). Here, we found that a TRPγ mutant exhibited in is required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) of . Interestingly, deficient mutants exhibited elevated TAG levels and our genetic data indicated that neurons are indispensable for normal lipid storage but not protein storage. The mutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated that knockout downregulated , a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulate nutrient storage.
了解大脑如何控制营养物质储存至关重要。瞬时受体电位（TRP）通道从昆虫到人类都保守存在。它们用于检测环境变化并充当内部传感器。此前，我们证明了TRPγ在营养感知行为中的作用（达卡尔等人，2022年）。在此，我们发现TRPγ突变体在维持正常脂质和蛋白质水平方面所表现出的某种情况是必需的。在动物中，脂肪生成和脂肪分解根据食物供应情况控制脂质水平。脂质大多以三酰甘油的形式储存在[此处原文缺失相关动物名称]的脂肪体（FBs）中。有趣的是，[此处原文缺失相关名称]缺陷突变体表现出三酰甘油水平升高，我们的遗传数据表明[此处原文缺失相关名称]神经元对于正常脂质储存不可或缺，但对蛋白质储存并非如此。[此处原文缺失相关名称]突变体还表现出饥饿抗性降低，这归因于脂肪体中脂肪分解不足。口服脂肪酶或二甲双胍可缓解这种情况，这表明了一种潜在的治疗途径。基因表达分析表明，[此处原文缺失相关名称]基因敲除下调了关键脂肪分解基因[此处原文缺失相关基因名称]，导致肠道和其他脂肪组织出现慢性脂肪分解缺陷。该研究还强调了特定蛋白质的作用，包括神经肽DH44及其受体DH44R2在脂质调节中的作用。我们的研究结果为大脑和肠道如何调节营养物质储存这一更广泛的问题提供了见解。
