BCAA catabolism in brown fat controls energy homeostasis through SLC25A44

Yoneshiro Takeshi; Wang Qiang; Tajima Kazuki; Matsushita Mami; Maki Hiroko; Igarashi Kaori; Dai Zhipeng; White Phillip J.; McGarrah Robert W.; Ilkayeva Olga R.; Deleye Yann; Oguri Yasuo; Kuroda Mito; Ikeda Kenji; Li Huixia; Ueno Ayano; Ohishi Maki; Ishikawa Takamasa; Kim Kyeongkyu; Chen Yong; Sponton Carlos Henrique; Pradhan Rachana N.; Majd Homa; Greiner Vanille Juliette; Yoneshiro Momoko; Brown Zachary; Chondronikola Maria; Takahashi Haruya; Goto Tsuyoshi; Kawada Teruo; Sidossis Labros; Szoka Francis C.; McManus Michael T.; Saito Masayuki; Soga Tomoyoshi; Kajimura Shingo

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BCAA catabolism in brown fat controls energy homeostasis through SLC25A44

机译：BCAA棕色脂肪的分解代谢控制能源稳态通过SLC25A44

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Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health.

机译：支链氨基酸（BCAA;缬氨酸，亮氨酸和异亮氨酸）补充通常有利于能源支出;然而，增加BCAA的循环水平与肥胖和糖尿病有关。这种悖论的机制仍然不清楚。在这里，我们报告称，在冷曝光时，棕色脂肪组织（BAT）积极利用BCAA在线粒体中进行热生成，促进小鼠和人类的全身BCAA间隙。反过来，BCAA分解代谢的BAT特异性缺陷衰减全身BCAA间隙，蝙蝠燃料氧化和热生成，导致饮食诱导的肥胖和葡萄糖不耐受。机械地，蝙蝠中的活性BCAA分解代谢由SLC25A44介导，将BCAAs转化为线粒体。我们的研究结果表明，BAT作为通过SLC25A44控制BCAA间隙的关键代谢滤波器，从而有助于改善代谢健康。

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《Nature》 |2019年第7771期|614-619|共6页
作者
Yoneshiro Takeshi; Wang Qiang; Tajima Kazuki; Matsushita Mami; Maki Hiroko; Igarashi Kaori; Dai Zhipeng; White Phillip J.; McGarrah Robert W.; Ilkayeva Olga R.; Deleye Yann; Oguri Yasuo; Kuroda Mito; Ikeda Kenji; Li Huixia; Ueno Ayano; Ohishi Maki; Ishikawa Takamasa; Kim Kyeongkyu; Chen Yong; Sponton Carlos Henrique; Pradhan Rachana N.; Majd Homa; Greiner Vanille Juliette; Yoneshiro Momoko; Brown Zachary; Chondronikola Maria; Takahashi Haruya; Goto Tsuyoshi; Kawada Teruo; Sidossis Labros; Szoka Francis C.; McManus Michael T.; Saito Masayuki; Soga Tomoyoshi; Kajimura Shingo;
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UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

Tenshi Coll Dept Nutr Sapporo Hokkaido Japan;

Keio Univ Inst Adv Biosci Yamagata Japan;

Keio Univ Inst Adv Biosci Yamagata Japan;

Univ Calif San Francisco Dept Bioengn & Therapeut Sci San Francisco CA 94143 USA;

Duke Univ Duke Mol Physiol Inst Durham NC USA;

Duke Univ Duke Mol Physiol Inst Durham NC USA;

Duke Univ Duke Mol Physiol Inst Durham NC USA;

Duke Univ Duke Mol Physiol Inst Durham NC USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA|Tokyo Med & Dent Univ Dept Mol Endocrinol & Metab Tokyo Japan;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

Keio Univ Inst Adv Biosci Yamagata Japan;

Keio Univ Inst Adv Biosci Yamagata Japan;

Keio Univ Inst Adv Biosci Yamagata Japan;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Univ Calif San Francisco Dept Microbiol & Immunol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

Washington Univ Ctr Human Nutr St Louis MO 63110 USA;

Kyoto Univ Lab Mol Funct Food Grad Sch Agr Uji Kyoto Japan;

Kyoto Univ Lab Mol Funct Food Grad Sch Agr Uji Kyoto Japan;

Kyoto Univ Lab Mol Funct Food Grad Sch Agr Uji Kyoto Japan;

Rutgers State Univ Dept Kinesiol & Hlth Sch Arts & Sci New Brunswick NJ USA;

Univ Calif San Francisco Dept Bioengn & Therapeut Sci San Francisco CA 94143 USA;

UCSF Diabet Ctr San Francisco CA 94143 USA|Univ Calif San Francisco Dept Microbiol & Immunol San Francisco CA 94143 USA;

Hokkaido Univ Dept Biomed Sci Grad Sch Vet Med Sapporo Hokkaido Japan;

Keio Univ Inst Adv Biosci Yamagata Japan;

UCSF Diabet Ctr San Francisco CA 94143 USA|Eli & Edythe Broad Ctr Regenerat Med & Stem Cell San Francisco CA 94131 USA|Univ Calif San Francisco Dept Cell & Tissue Biol San Francisco CA 94143 USA;

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1. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44 [J] . Yoneshiro Takeshi, Wang Qiang, Tajima Kazuki, Nature . 2019,第7771期

机译：棕色脂肪中的BCAA分解代谢通过SLC25A44控制能量稳态
2. A New Era in Brown Adipose Tissue Biology: Molecular Control of Brown Fat Development and Energy Homeostasis [J] . Shingo Kajimura Masayuki Saito Annual Review of Physiology . 2014,第Null期

机译：棕色脂肪组织生物学的新纪元：棕色脂肪发育和能量稳态的分子控制
3. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis [J] . Labros Sidossis, Shingo Kajimura The journal of clinical investigation . 2015,第2期

机译：人类的棕色和米色脂肪：控制能量和葡萄糖稳态的产热脂肪细胞
4. Catabolism of brown coal macromolecules by the white-rot fungus Phanerochaete chrysosporium [C] . J.P. Ralph, D.E.A. Catcheside International conference on coal science;ICCS '97 . 1997

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5. Octacosanol prevents high fat diet-induced obesity by activating energy expenditure and thermogenesis in brown and beige fats [D] . Rahul Sharma 2019

机译：十八碳烷醇可通过激活棕色和米色脂肪中的能量消耗和生热作用来预防高脂饮食引起的肥胖
6. A New Era in Brown Adipose Tissue Biology: Molecular Control of Brown Fat Development and Energy Homeostasis [O] . Shingo Kajimura, Masayuki Saito -1

机译：棕色脂肪组织生物学的新纪元：棕色脂肪发育和能量稳态的分子控制
7. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44 [O] . Takeshi Yoneshiro, Qiang Wang, Kazuki Tajima, 2019

机译：BCAA棕色脂肪的分解代谢控制能源稳态通过SLC25A44

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44

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