白色脂肪细胞对较低温度的适应：对能量代谢和蛋白质乙酰化的影响
Adaptation of White Adipocytes to Cooler Temperatures: Impacts on Energy Metabolism and Protein Acetylation.
摘要(中文译文)
全身脂肪细胞处于不同的温度环境中。位于身体核心的内脏脂肪细胞维持在接近37°C，而骨髓、皮下和真皮脂肪库中的脂肪细胞则位于外周壳层较冷的区域。尽管棕色和米色脂肪细胞对冷应激的反应已被充分表征，但关于白色脂肪细胞如何适应低于37°C的适度降温却知之甚少。我们近期的工作发现，暴露于31°C（代表远端脂肪区域温度）的培养脂肪细胞表现出线粒体功能增强，包括底物氧化和ATP周转增加，然而这种上调背后的机制仍不清楚。在此我们表明，适应较冷温度导致未分化和分化脂肪细胞中蛋白质乙酰化广泛降低，且不依赖于营养状态，并且这种变化在复温后易于逆转。亚细胞分级分离和免疫印迹显示，低乙酰化与线粒体内乙酰化蛋白的区室特异性富集同时发生，表明线粒体乙酰化组的选择性重塑。转录组学和生化分析揭示，这些温度依赖性变化不伴随乙酰转移酶或去乙酰化酶表达、NAD浓度或乙酰辅酶A可用性的改变，提示其通过影响乙酰辅酶A通量或酶活性的替代机制进行调控。整合乙酰化蛋白质组学和代谢组学分析鉴定出线粒体酶，包括丝氨酸羟甲基转移酶2（SHMT2）和丙酰辅酶A羧化酶α（PCCA），其乙酰化与相关代谢物池的变化密切相关。总之，这些发现确立了生理相关降温作为脂肪细胞线粒体蛋白乙酰化和代谢适应的细胞自主调节因素。
Abstract
Adipocytes throughout the body reside in distinct thermal environments. Visceral adipocytes within the body core are maintained near 37°C, whereas those in bone marrow, subcutaneous, and dermal depots occupy cooler regions within the peripheral shell. Although brown and beige adipocyte responses to cold stress are well characterized, much less is known about how white adipocytes adapt to moderately reduced temperatures below 37°C. Our recent work revealed that cultured adipocytes exposed to 31°C, a temperature representative of distal adipose regions, exhibit enhanced mitochondrial function, including increased substrate oxidation and ATP turnover, yet the mechanisms underlying this upregulation remain unclear. Here we show that adaptation to cool temperatures leads to a widespread decrease in protein acetylation in both undifferentiated and differentiated adipocytes, independent of nutrient status, and that this change is readily reversible upon rewarming. Subcellular fractionation and immunoblotting demonstrate that the hypoacetylation coincides with a compartment-specific enrichment of acetylated proteins within mitochondria, indicating selective remodeling of the mitochondrial acetylome. Transcriptomic and biochemical analyses reveal that these temperature-dependent changes occur without alterations in acetyltransferase or deacetylase expression, NAD concentration, or acetyl-CoA availability, suggesting regulation through alternative mechanisms affecting acetyl-CoA flux or enzyme activity. Integrative acetyl-proteomic and metabolomic profiling identifies mitochondrial enzymes, including serine hydroxymethyltransferase 2 (SHMT2) and propionyl-CoA carboxylase α (PCCA), whose acetylation correlates closely with changes in associated metabolite pools. Together, these findings establish physiologically relevant cooling as a cell-autonomous regulator of mitochondrial protein acetylation and metabolic adaptation in adipocytes.
如何引用
AMA
Hiroyuki Mori, Hadla Hariri, William Moe, Sophia Durham, Yuridia Guzman, Emma Paulsson, et al. Adaptation of White Adipocytes to Cooler Temperatures: Impacts on Energy Metabolism and Protein Acetylation.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2026; doi:10.1096/fj.202601941R.
APA
Hiroyuki Mori, Hadla Hariri, William Moe, Sophia Durham, Yuridia Guzman, Emma Paulsson, et al (2026). Adaptation of White Adipocytes to Cooler Temperatures: Impacts on Energy Metabolism and Protein Acetylation.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202601941R
GB/T 7714
Hiroyuki Mori, Hadla Hariri, William Moe, Sophia Durham, Yuridia Guzman, Emma Paulsson, et al. Adaptation of White Adipocytes to Cooler Temperatures: Impacts on Energy Metabolism and Protein Acetylation.[J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026 doi:10.1096/fj.202601941R.
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