<p>Brown adipose tissue (BAT) contributes to thermoregulation and glucose metabolism, but how these functions are coordinated remains unclear. While thermogenesis in the activated BAT typically coincides with increased blood flow and glucose uptake<sup><CitationRef AdditionalCitationIDS="CR2 CR3 CR4" CitationID="CR1">1</CitationRef>–<CitationRef CitationID="CR5">5</CitationRef></sup>, several pathophysiological and nutritional states dissociate these processes<sup><CitationRef CitationID="CR6">6</CitationRef>,<CitationRef CitationID="CR7">7</CitationRef></sup>, suggesting they are governed by distinct sympathetic circuits. Here we identify subpopulations of sympathetic neurons in the stellate ganglion that mediate distinct functions of intrascapular BAT (iBAT) in mice. Two main types of sympathetic neurons project to iBAT: those that innervate the organ parenchyma and those that innervate the large blood vessels feeding the depot<sup><CitationRef AdditionalCitationIDS="CR9 CR10 CR11" CitationID="CR8">8</CitationRef>–<CitationRef CitationID="CR12">12</CitationRef></sup>. Here we develop a toolkit to parse the functions of these neuronal subclasses through targeted chemogenetic activation of projections to iBAT, while sparing other organs, and single-cell transcriptomics coupled to retrograde tracing from iBAT to the stellate ganglion. We find that stimulation of the parenchymal projections increases blood flow and thermogenesis in iBAT, without affecting circulating glucose levels. Conversely, stimulation of the vascular projections improves glucose tolerance but does not alter blood flow or thermogenesis in iBAT. These data provide a mechanistic explanation for the dissociation between the thermogenic and glycaemic effects of BAT activation<sup><CitationRef AdditionalCitationIDS="CR14 CR15" CitationID="CR13">13</CitationRef>–<CitationRef CitationID="CR16">16</CitationRef></sup>.</p>

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Distinct sympathetic projections to brown fat regulate thermogenesis and glucose tolerance

  • Daniele Neri,
  • Seoeun Lee,
  • Alexis M. Fohn,
  • Xinhong Chen,
  • Dominique Bozec,
  • Alexandre J. Lafond,
  • Natalie R. Lopatinsky,
  • Lucas Castro e Souza,
  • Gawri Mohanan Nair,
  • Angela M. Ramos-Lobo,
  • Markus Heine,
  • Anna Worthmann,
  • Joerg Heeren,
  • Vidhu V. Thaker,
  • Viviana Gradinaru,
  • Lori M. Zeltser

摘要

Brown adipose tissue (BAT) contributes to thermoregulation and glucose metabolism, but how these functions are coordinated remains unclear. While thermogenesis in the activated BAT typically coincides with increased blood flow and glucose uptake15, several pathophysiological and nutritional states dissociate these processes6,7, suggesting they are governed by distinct sympathetic circuits. Here we identify subpopulations of sympathetic neurons in the stellate ganglion that mediate distinct functions of intrascapular BAT (iBAT) in mice. Two main types of sympathetic neurons project to iBAT: those that innervate the organ parenchyma and those that innervate the large blood vessels feeding the depot812. Here we develop a toolkit to parse the functions of these neuronal subclasses through targeted chemogenetic activation of projections to iBAT, while sparing other organs, and single-cell transcriptomics coupled to retrograde tracing from iBAT to the stellate ganglion. We find that stimulation of the parenchymal projections increases blood flow and thermogenesis in iBAT, without affecting circulating glucose levels. Conversely, stimulation of the vascular projections improves glucose tolerance but does not alter blood flow or thermogenesis in iBAT. These data provide a mechanistic explanation for the dissociation between the thermogenic and glycaemic effects of BAT activation1316.