Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism
| Autor: | Mishra, D., Richard, J.E., Maric, I., Porteiro, B., Haring, M., Kooijman, S., Musovic, S., Eerola, K., Lopez-Ferreras, L., Peris, E., Grycel, K., Shevchouk, O.T., Micallef, P., Olofsson, C.S., Asterholm, I.W., Grill, H.J., Nogueiras, R., Skibicka, K.P. |
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| Přispěvatelé: | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Fisioloxía |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Leptin
Male sex differences Thyroid Hormones obesity Sympathetic Nervous System diet-induced obesity Cold exposure cold exposure Energy balance Brown adipose tissue Article thyroid Rats Sprague-Dawley Eating Mice Adipose Tissue Brown Sex differences Animals Obesity lcsh:QH301-705.5 Neurons Thyroid Interleukin-6 Body Weight lateral PBN Diet-induced obesity Thermogenesis brown adipose tissue Parabrachial Nucleus Hindbrain energy balance Rats Mice Inbred C57BL lcsh:Biology (General) Astrocytes Female PVN Energy Metabolism Lateral PBN hindbrain |
| Zdroj: | Cell Reports, 26(11), 3011-+. CELL PRESS Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname Cell Reports, Vol 26, Iss 11, Pp 3011-3026.e5 (2019) Cell Reports |
| Popis: | Summary Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6. Graphical Abstract Highlights • Obesogenic diet robustly reduces, and 4°C cold exposure increases, rodent lPBN IL-6 • IL-6 interacts with leptin at the level of the lPBN to reduce food intake • LPBN IL-6 leads to increased BAT thermogenesis by thyroid and sympathetic mechanisms • Reduction in lPBN IL-6 increases weight gain and adiposity Mishra et al. demonstrate that IL-6 is produced by lPBN neurons, astrocytes, and microglia. They show that IL-6 acts in the lPBN to reduce body weight by increasing thermogenesis and reducing food intake. They also identify two pathophysiological/physiological contexts, obesity and cold exposure, that divergently affect lPBN IL-6 production. |
| Databáze: | OpenAIRE |
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