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1.
Immunity ; 57(1): 141-152.e5, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38091996

RESUMEN

Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reduction of fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatory leptin receptor-positive (LepR+) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquely co-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33 in SPCs (SPCΔIl33) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BAT inflammation. SPCΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPCΔIl33 mice had impaired adaptive thermogenesis and were unresponsive to leptin-induced rescue of metabolic adaptation. We therefore identify LepR+ SPCs as a source of IL-33, which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR+IL-33+ SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research.


Asunto(s)
Tejido Adiposo Pardo , Leptina , Animales , Humanos , Ratones , Tejido Adiposo Pardo/inervación , Tejido Adiposo Pardo/metabolismo , Peso Corporal , Metabolismo Energético/fisiología , Interleucina-33/genética , Interleucina-33/metabolismo , Obesidad/metabolismo , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Termogénesis/fisiología
2.
J Am Chem Soc ; 143(18): 6836-6846, 2021 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-33939921

RESUMEN

Optical imaging within the shortwave infrared (SWIR, 1000-2000 nm) region of the electromagnetic spectrum has enabled high-resolution and high-contrast imaging in mice, non-invasively. Polymethine dyes, with their narrow absorption spectra and high absorption coefficients, are optimal probes for fast and multiplexed SWIR imaging. Here, we expand upon the multiplexing capabilities in SWIR imaging by obtaining brighter polymethine dyes with varied excitation wavelengths spaced throughout the near-infrared (700-1000 nm) region. Building on the flavylium polymethine dye scaffold, we explored derivatives with functional group substitution at the 2-position, deemed chromenylium polymethine dyes. The reported dyes have reduced nonradiative rates and enhanced emissive properties, enabling non-invasive imaging in mice in a single color at 300 fps and in three colors at 100 fps. Combined with polymethine dyes containing a red-shifted julolidine flavylium heterocycle and indocyanine green, distinct channels with well-separated excitation wavelengths provide non-invasive video-rate in vivo imaging in four colors.


Asunto(s)
Color , Colorantes Fluorescentes/química , Indoles/química , Imagen Óptica , Animales , Colorantes Fluorescentes/síntesis química , Indoles/síntesis química , Rayos Infrarrojos , Ratones , Estructura Molecular
3.
ACS Nano ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264287

RESUMEN

This article represents the first foray into investigating the consequences of various material combinations on the short-wave infrared (SWIR, 1000-2000 nm) performance of Tm-based core-shell nanocrystals (NCs) above 1600 nm. In total, six different material combinations involving two different types of SWIR-emitting core NCs (α-NaTmF4 and LiTmF4) combined with three different protecting shell materials (α-NaYF4, CaF2, and LiYF4) have been synthesized. All corresponding homo- and heterostructured NCs have been meticulously characterized by powder X-ray diffraction and electron microscopy techniques. The latter revealed that out of the six investigated combinations, only one led to the formation of a true core-shell structure with well-segregated core and shell domains. The direct correlation between the downshifting performance and the spatial localization of Tm3+ ions within the final homo- and heterostructured NCs is established. Interestingly, to achieve the best SWIR performance, the formation of an abrupt interface is not a prerequisite, while the existence of a pure (even thin) protective shell is vital. Remarkably, although all homo- and heterostructured NCs have been synthesized under the exact same experimental conditions, Tm3+ SWIR emission is either fully quenched or highly efficient depending on the type of material combination. The most efficient combination (LiTmF4/LiYF4) achieved a high photoluminescence quantum yield of 39% for SWIR emission above 1600 nm (excitation power density in the range 0.5-3 W/cm2) despite significant intermixing. From now on, highly efficient SWIR-emitting probes with an emission above 1600 nm are within reach to unlock the full potential of in vivo SWIR imaging.

4.
Front Neurosci ; 17: 1135494, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37274204

RESUMEN

Extracting biological information from awake and unrestrained mice is imperative to in vivo basic and pre-clinical research. Accordingly, imaging methods which preclude invasiveness, anesthesia, and/or physical restraint enable more physiologically relevant biological data extraction by eliminating these extrinsic confounders. In this article, we discuss the recent development of shortwave infrared (SWIR) fluorescent imaging to visualize peripheral organs in freely-behaving mice, as well as propose potential applications of this imaging modality in the neurosciences.

5.
bioRxiv ; 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37163051

RESUMEN

Extracting biological information from awake and unrestrained mice is imperative to in vivo basic and pre-clinical research. Accordingly, imaging methods which preclude invasiveness, anesthesia, and/or physical restraint enable more physiologically relevant biological data extraction by eliminating these extrinsic confounders. In this article we discuss the recent development of shortwave infrared (SWIR) fluorescent imaging to visualize peripheral organs in freely-behaving mice, as well as propose potential applications of this imaging modality in the neurosciences.

6.
Nat Commun ; 14(1): 4462, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37491427

RESUMEN

Short-wave infrared (SWIR) fluorescence could become the new gold standard in optical imaging for biomedical applications due to important advantages such as lack of autofluorescence, weak photon absorption by blood and tissues, and reduced photon scattering coefficient. Therefore, contrary to the visible and NIR regions, tissues become translucent in the SWIR region. Nevertheless, the lack of bright and biocompatible probes is a key challenge that must be overcome to unlock the full potential of SWIR fluorescence. Although rare-earth-based core-shell nanocrystals appeared as promising SWIR probes, they suffer from limited photoluminescence quantum yield (PLQY). The lack of control over the atomic scale organization of such complex materials is one of the main barriers limiting their optical performance. Here, the growth of either homogeneous (α-NaYF4) or heterogeneous (CaF2) shell domains on optically-active α-NaYF4:Yb:Er (with and without Ce3+ co-doping) core nanocrystals is reported. The atomic scale organization can be controlled by preventing cation intermixing only in heterogeneous core-shell nanocrystals with a dramatic impact on the PLQY. The latter reached 50% at 60 mW/cm2; one of the highest reported PLQY values for sub-15 nm nanocrystals. The most efficient nanocrystals were utilized for in vivo imaging above 1450 nm.

7.
Nat Chem ; 12(12): 1123-1130, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33077925

RESUMEN

High-resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to substantial scattering and autofluorescence in tissue at visible (350-700 nm) and near-infrared (700-1,000 nm) wavelengths. Here, we enable real-time, non-invasive multicolour imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000-2,000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established relationships between structure and photophysical properties for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable near-infrared/SWIR excitation and single-channel detection, facilitating video-rate multicolour SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1,064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-colour imaging with high temporal and spatial resolutions.


Asunto(s)
Benzopiranos/química , Medios de Contraste/química , Colorantes Fluorescentes/química , Imagen Óptica/métodos , Animales , Benzopiranos/síntesis química , Benzopiranos/efectos de la radiación , Medios de Contraste/síntesis química , Medios de Contraste/efectos de la radiación , Femenino , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Rayos Infrarrojos , Rayos Láser , Ratones Desnudos , Imagen Óptica/instrumentación
8.
Nat Med ; 23(11): 1309-1318, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29035364

RESUMEN

The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron-associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment.


Asunto(s)
Macrófagos/metabolismo , Neuronas/metabolismo , Norepinefrina/metabolismo , Obesidad/patología , Sistema Nervioso Simpático/patología , Animales , Receptor 1 de Quimiocinas CX3C/metabolismo , Perfilación de la Expresión Génica , Homeostasis , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Obesidad/genética
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