Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride–glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo. Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism.

中文翻译：

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胰岛素信号需要葡萄糖来促进脂肪细胞中的脂质合成代谢。

脂肪组织对于代谢稳态、根据营养状况平衡脂质储存和动员至关重要。这是由胰岛素协调的，胰岛素触发激酶信号级联以调节多种代谢蛋白，导致葡萄糖摄取增加和合成代谢过程，如脂肪生成。鉴于最近有证据表明葡萄糖对于脂肪细胞呼吸是可有可无的，我们试图测试葡萄糖是否是胰岛素刺激合成代谢所必需的。检查培养的脂肪细胞中的脂肪生成，葡萄糖对于胰岛素刺激脂肪酸和甘油酯 - 甘油的合成是必不可少的。重要的是，在没有胰岛素的情况下，葡萄糖对于脂肪生成是可有可无的，这表明在有或没有胰岛素的情况下使用不同的碳源。代谢追踪研究表明，胰岛素需要葡萄糖来刺激为脂质合成和储存提供碳底物、NADPH 和 3-磷酸甘油的途径。葡萄糖还取代亮氨酸作为脂肪生成底物，并且是抑制脂肪酸氧化所必需的。总之，葡萄糖为胰岛素提供了底物和代谢控制，以促进脂肪细胞的脂肪生成。这与胰岛素信号传导抑制脂肪分解形成对比，后者独立于葡萄糖发生。鉴于先前观察到信号转导主要在脂肪细胞摄取葡萄糖之前起作用，这些数据与胰岛素最初利用蛋白质磷酸化来刺激脂质合成代谢的模型一致，该合成代谢由随后的葡萄糖代谢维持。最后，脂质丰度对葡萄糖可用性敏感，无论是在脂肪生成过程中还是在体内果蝇中。总之，这些数据突出了葡萄糖代谢对支持胰岛素作用的重要性，为信号转导提供了补充调节机制以刺激脂肪合成代谢。