Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.
Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.
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DOI：
10.1016/j.celrep.2022.111187
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发表时间：
2022-08-16
期刊：
影响因子：
8.8
通讯作者：
Mitchell, James R.
中科院分区：
文献类型：
--
作者：
MacArthur, Michael R.;Mitchell, Sarah J.;Chadaideh, Katia S.;Trevino-Villarreal, J. Humberto;Jung, Jonathan;Kalafut, Krystle C.;Reynolds, Justin S.;Mann, Charlotte G.;Trocha, Kaspar M.;Tao, Ming;Aye, Tay-Zar;Koontanatechanon, Anantawat;Yeliseyev, Vladimir;Bry, Lynn;Longchamp, Alban;Ozaki, C. Keith;Lewis, Caroline A.;Carmody, Rachel N.;Mitchell, James R.
膳食蛋白限制（PR）通过多种机制对代谢产生快速影响，包括改善葡萄糖和脂质稳态。在这里，我们研究了粪便微生物组，肝脏转录组和肝脏代谢组对小鼠中蛋白质占能量18%至0%的六种饮食的反应。PR改变粪便微生物组成，但代谢效应不能通过粪便移植转移。在蛋白质能量低于10%的饮食中，肝脏转录组和代谢组显著改变。PR的变化与热量限制相关，但与氨基酸（AA）代谢的更大幅度和特定变化相关。PR增加稳态天冬氨酸、丝氨酸和谷氨酸，并减少葡萄糖和代谢中间体。13C6葡萄糖和甘油示踪显示天冬氨酸、丝氨酸和谷氨酸的富集分数增加。在肝ATF4敲除小鼠中变化保持完整。总之，这表明了一个ATF4独立的转变，在致炎性底物利用特定的AA，从甘油的补偿，以促进蛋白质节约的反应。麦克阿瑟等人使用多种无偏方法研究了小鼠在6个饮食蛋白质限制水平下的代谢和分子反应。作者表明，许多关键的肝脏反应发生在低于10%蛋白质能量的情况下，并促进葡萄糖代谢的ATF 4非依赖性重新布线，以支持丝氨酸、天冬氨酸和谷氨酸合成。
Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation. Hepatic transcriptome and metabolome are significantly altered in diets with lower than 10% energy from protein. Changes upon PR correlate with calorie restriction but with a larger magnitude and specific changes in amino acid (AA) metabolism. PR increases steady-state aspartate, serine, and glutamate and decreases glucose and gluconeogenic intermediates. 13C6 glucose and glycerol tracing reveal increased fractional enrichment in aspartate, serine, and glutamate. Changes remain intact in hepatic ATF4 knockout mice. Together, this demonstrates an ATF4-independent shift in gluconeogenic substrate utilization toward specific AAs, with compensation from glycerol to promote a protein-sparing response. MacArthur et al. use multiple unbiased methods to investigate metabolic and molecular responses across six levels of dietary protein restriction in mice. The authors show that many key hepatic responses occur below 10% protein energy and promote ATF4-independent rewiring of glucose metabolism to support serine, aspartate, and glutamate synthesis.
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影响因子：
3.7
作者：
Gosby AK;Lau NS;Tam CS;Iglesias MA;Morrison CD;Caterson ID;Brand-Miller J;Conigrave AD;Raubenheimer D;Simpson SJ
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