期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 111, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2022.109083
关键词
Hypothalamic inflammation; Sodium butyrate; Microglia; Neuron
资金
- Natural Science Foundation of Jiangsu Province [BK20211108]
- National Natural Science Youth Fund of China [32101027]
- Scientific Research Project of Health Commission of Jiangsu Province [M2021106]
- Nantong Science and Technology Project [JC2021015, JC2021001]
- Nantong Municipal Commission of Health and Family Planning [QB2021003, MA2021012]
This study reveals the anti-inflammatory and antioxidant effects of sodium butyrate (NaB) in overnutrition-induced microglial activation and hypothalamic inflammation.
Overnutrition-induced hypothalamic inflammation greatly disturbs feeding behavior and energy homeostasis as well as the pathogenesis of obesity. Butyrate, a short-chain fatty acid, reportedly participates in the regulation of the immune response and energy metabolism in the body. However, the role of butyrate in overnutrition-induced microglial activation and hypothalamic inflammation remains unclear. In the present study, we established a high-fat diet (HFD)-induced hypothalamic inflammation model in mice. Oral supplementation with sodium butyrate (NaB) significantly reduced HFD-induced microgliosis, inflammatory cytokine expression, endoplasmic reticulum (ER) stress, neuronal apoptosis, and neuropeptide Y (NPY) expression in the mouse hypothalamus. Utilizing a high-glucose (HG)-stimulated microglial activation model in vitro, we found that NaB inhibited the HG-induced expression of the inflammatory factor IL-1 beta. Moreover, NaB exerted an antioxidant effect by balancing HO-1 and NOX4 expression, thus preventing reactive oxygen species (ROS) production in HG-treated microglia. Interestingly, NaB treatment promoted microglial process formation and extension via the Akt/Cdc42 pathway under both normal and HG-stimulated conditions, indicating a resting morphology of microglia. Taken together, our study revealed for the first time the anti-inflammatory and antioxidant effects of NaB in overnutrition-induced microglial activation and hypothalamic inflammation, which might become a potential therapeutic option for obesity prevention and treatment.
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