Sodium butyrate reduces 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-1ß. 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.

Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries.

The fecundity of female mammals is resolved by the limited size of the primordial follicle (PF) pool formed perinatally. The establishment of PF pool is accompanied by a significant programmed oocyte death. Long non-coding RNAs (lncRNA) are central modulators in regulating cell apoptosis or autophagy in multiple diseases, however, the significance of lncRNAs governing perinatal oocyte loss remains unknown. Here we find that Yin-Yang 1 (YY1) directly binds to the lncRNA X-inactive-specific transcript (Xist) promoter and facilitates Xist expression in the perinatal mouse ovaries. Xist is highly expressed in fetal ovaries and sharply downregulated along with the establishment of PF pool after birth. Gain or loss of function analysis reveals that Xist accelerates oocyte autophagy, mainly through binding to pre-miR-23b or pre-miR-29a in the nucleus and preventing the export of pre-miR-23b/pre-miR-29a to the cytoplasm, thus resulting in decreased mature of miR-23b-3p/miR-29a-3p expression and upregulation miR-23b-3p/miR-29a-3p co-target, STX17, which is essential for timely control of the degree of oocyte death in prenatal mouse ovaries. Overall, these findings identify Xist as a key non-protein factor that can control the biogenesis of miR-23b-3p/miR-29a-3p, and this YY1-Xist-miR-23b-3p/miR-29a-3p-STX17 regulatory axis is responsible for perinatal oocyte loss through autophagy.