KLF15 controls brown adipose tissue transcriptional flexibility and metabolism in response to various energetic demands.
KLF15 controls brown adipose tissue transcriptional flexibility and metabolism in response to various energetic demands.
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DOI：
10.1016/j.isci.2022.105292
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发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Jain, Mukesh K.
中科院分区：
文献类型：
--
作者：
Fan, Liyan;Lesser, Alexander F.;Sweet, David R.;Keerthy, Komal S.;Lu, Yuan;Chan, Ernest R.;Vinayachandran, Vinesh;Ilkayeva, Olga;Das, Tapatee;Newgard, Christopher B.;Jain, Mukesh K.
棕色脂肪组织（BAT）是一种专门的代谢器官，负责非颤抖性产热。最近，它的活性已被证明是至关重要的全身代谢健康，通过其利用和消费的宏量营养素。面对能量要求很高的状态，代谢灵活性和营养分配的系统协调对于健康和生存是必要的。在这项研究中，我们阐明了BAT的差异转录适应多种营养的挑战，并证明其上下文依赖的脂质，葡萄糖和氨基酸代谢的优先顺序。我们发现，转录因子Krüppel样因子15（KLF 15）在BAT代谢灵活性中起着关键作用。BAT特异性KLF 15的丢失导致循环代谢物的广泛变化，并严重损害了对高能量需求的产热作用，表明营养利用和代谢灵活性受损。总之，我们的数据表明BAT中的KLF 15在分配资源以维持稳态和确保生存方面发挥着不可或缺的作用。KLF 15是BAT产热和代谢的关键调节因子BAT在转录上优先于禁食的产热BAT代谢灵活性因KLF 15缺陷而显着受损BAT KLF 15敲除改变循环脂质和氨基酸人类代谢;分子生物学;细胞生物学。
Brown adipose tissue (BAT) is a specialized metabolic organ responsible for non-shivering thermogenesis. Recently, its activity has been shown to be critical in systemic metabolic health through its utilization and consumption of macronutrients. In the face of energetically demanding states, metabolic flexibility and systemic coordination of nutrient partitioning is requisite for health and survival. In this study, we elucidate BAT’s differential transcriptional adaptations in response to multiple nutrient challenges and demonstrate its context-dependent prioritization of lipid, glucose, and amino acid metabolism. We show that the transcription factor Krüppel-like factor 15 (KLF15) plays a critical role in BAT metabolic flexibility. BAT-specific loss of KLF15 results in widespread changes in circulating metabolites and severely compromised thermogenesis in response to high energy demands, indicative of impaired nutrient utilization and metabolic flexibility. Together, our data demonstrate KLF15 in BAT plays an indispensable role in partitioning resources to maintain homeostasis and ensure survival. KLF15 is a critical regulator of BAT thermogenesis and metabolism BAT transcriptionally prioritizes thermogenesis over fasting BAT metabolic flexibility is significantly impaired with KLF15 deficiency BAT KLF15 knockout alters circulating lipids and amino acids Human metabolism; Molecular biology; Cell biology.
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影响因子：
7.7
作者：
Saito M;Okamatsu-Ogura Y;Matsushita M;Watanabe K;Yoneshiro T;Nio-Kobayashi J;Iwanaga T;Miyagawa M;Kameya T;Nakada K;Kawai Y;Tsujisaki M
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Tsujisaki M
影响因子：
3.7
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Khomtchouk, Bohdan B.;Hennessy, James R.;Wahlestedt, Claes
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Wahlestedt, Claes
影响因子：
4.5
作者：
Ferrara CT;Wang P;Neto EC;Stevens RD;Bain JR;Wenner BR;Ilkayeva OR;Keller MP;Blasiole DA;Kendziorski C;Yandell BS;Newgard CB;Attie AD
通讯作者：
Attie AD
影响因子：
5.2
作者：
Machado FSM;Zhang Z;Su Y;de Goede P;Jansen R;Foppen E;Coimbra CC;Kalsbeek A
通讯作者：
Kalsbeek A
影响因子：
18.2
作者：
Kajimura S;Saito M
通讯作者：
Saito M