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Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons

机译：Opsin 5下丘脑神经元的紫光抑制热生成

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摘要

Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light(1,2). In mice, OPN5 is a known photoreceptor in the retina(3)and skin(4)but is also expressed in the hypothalamic preoptic area (POA)(5). Here we describe a light-sensing pathway in which POA neurons that expressOpn5regulate thermogenesis in brown adipose tissue (BAT). We show thatOpn5is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show thatOpn5POA neurons project to BAT and decrease its activity under chemogenetic stimulation.Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not inOpn5-null mice. Direct measurements of intracellular cAMP ex vivo show thatOpn5POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.
机译：小鼠在紫罗兰色敏感的下丘脑的沉疗区域中具有神经元;这些深脑神经元感测通过OPN5光，并调节棕色脂肪中的自适应热生成。蛋白偶联受体的Opsin家族用作动物中的光探测器。 OPSIN 5（也称为神经用作蛋白酶或OPN5）是一种高度保守的OPSIN，对可见紫光（1,2）敏感。在小鼠中，OPN5是视网膜（3）和皮肤（4）中的已知感光体，但也在下丘脑近疗区域（POA）（5）中表达。在这里，我们描述了一种光传感途径，其中POA神经元在棕色脂肪组织（BAT）中表达热生成。我们展示了在谷氨酸谷氨宫的谷氨酸剂温度感测Poa神经元中表达的Opn5is，其接受来自几个热调节核的突触输入。我们进一步向蝙蝠展示了opn5poa神经元项目，并在化学刺激下降低其活性。在冷攻击时，NO 5-null小鼠展示过度活跃的蝙蝠，增加体温和夸大的热生成。此外，冷曝光期间的紫色光致刺激急性抑制野生型小鼠中的蝙蝠温度，但不是inopn5-null小鼠。在紫罗兰光刺激时，Exvo的直接测量exvivo展示了CANDN5POA神经元增加营地。因此，该分析鉴定了通常抑制蝙蝠热量的紫色光敏深脑感光体。

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  • 来源
    《Nature》 |2020年第7825期|420-425|共6页
  • 作者

    Zhang Kevin X.; DSouza Shane; Upton Brian A.; Kernodle Stace; Vemaraju Shruti; Nayak Gowri; Gaitonde Kevin D.; Holt Amanda L.; Linne Courtney D.; Smith April N.; Petts Nathan T.; Batie Matthew; Mukherjee Rajib; Tiwari Durgesh; Buhr Ethan D.; Van Gelder Russell N.; Gross Christina; Sweeney Alison; Sanchez-Gurmaches Joan; Seeley Randy J.; Lang Richard A.;

  • 作者单位

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Mol & Dev Biol Grad Program Cincinnati OH USA|Univ Cincinnati Coll Med Med Sci Training Program Cincinnati OH USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Mol & Dev Biol Grad Program Cincinnati OH USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Mol & Dev Biol Grad Program Cincinnati OH USA|Univ Cincinnati Coll Med Med Sci Training Program Cincinnati OH USA;

    Univ Michigan Sch Publ Hlth Dept Surg Ann Arbor MI 48109 USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Mol & Dev Biol Grad Program Cincinnati OH USA|Univ Cincinnati Coll Med Med Sci Training Program Cincinnati OH USA;

    Yale Univ Dept Phys New Haven CT USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Mol & Dev Biol Grad Program Cincinnati OH USA|Univ Cincinnati Coll Med Med Sci Training Program Cincinnati OH USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Div Clin Engn Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Div Clin Engn Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Div Endocrinol Cincinnati OH 45229 USA;

    Cincinnati Childrens Hosp Med Ctr Div Neurol Cincinnati OH 45229 USA;

    Univ Washington Dept Ophthalmol Med Sch Seattle WA 98195 USA;

    Univ Washington Dept Ophthalmol Med Sch Seattle WA 98195 USA|Univ Washington Dept Biol Struct Med Sch Seattle WA 98195 USA|Univ Washington Dept Pathol Med Sch Seattle WA 98195 USA;

    Cincinnati Childrens Hosp Med Ctr Div Neurol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Dept Pediat Cincinnati OH USA;

    Yale Univ Dept Phys New Haven CT USA;

    Cincinnati Childrens Hosp Med Ctr Div Endocrinol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Dept Pediat Cincinnati OH USA|Cincinnati Childrens Hosp Med Ctr Div Dev Biol Cincinnati OH 45229 USA;

    Univ Michigan Sch Publ Hlth Dept Surg Ann Arbor MI 48109 USA|Univ Michigan Sch Publ Hlth Dept Internal Med Ann Arbor MI 48109 USA;

    Cincinnati Childrens Hosp Med Ctr Abrahamson Pediat Eye Inst Visual Syst Grp Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Ctr Chronobiol Div Pediat Ophthalmol Cincinnati OH 45229 USA|Cincinnati Childrens Hosp Med Ctr Div Dev Biol Cincinnati OH 45229 USA|Univ Cincinnati Coll Med Dept Ophthalmol Cincinnati OH 45221 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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