Hypothalamic perineuronal nets are regulated by sex and dietary interventions

Authors: ZHANG, NAN - Children'S Nutrition Research Center (CNRC); YAN, ZILI - Children'S Nutrition Research Center (CNRC); LIU, HAILAN - Children'S Nutrition Research Center (CNRC); YU, MENG - Children'S Nutrition Research Center (CNRC); HE, YANG - Children'S Nutrition Research Center (CNRC); LIU, HESONG - Children'S Nutrition Research Center (CNRC); LIANG, CHEN - Children'S Nutrition Research Center (CNRC); TU, LONGLONG - Children'S Nutrition Research Center (CNRC); WANG, LINA - Children'S Nutrition Research Center (CNRC); YIN, NA - Children'S Nutrition Research Center (CNRC); HAN, JUNYING - Children'S Nutrition Research Center (CNRC); SCARCELLI, NIKOLAS - Children'S Nutrition Research Center (CNRC); YANG, YONGJIE - Children'S Nutrition Research Center (CNRC); WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC); ZENG, TIANSHU - Huazhong University Of Science And Technology; CHEN, LU-LU - Huazhong University Of Science And Technology; XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Frontiers in Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/9/2021
Publication Date: 7/28/2021
Citation: Zhang, N., Yan, Z., Liu, H., Yu, M., He, Y., Liu, H., Liang, C., Tu, L., Wang, L., Yin, N., Han, J., Scarcelli, N., Yang, Y., Wang, C., Zeng, T., Chen, L., Xu, Y. 2021. Hypothalamic perineuronal nets are regulated by sex and dietary interventions. Frontiers in Physiology. 12. Article 714104. https://doi.org/10.3389/fphys.2021.714104.
DOI: https://doi.org/10.3389/fphys.2021.714104

Interpretive Summary: Recent evidence indicates that perineuronal nets (PNNs) in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated is not fully understood. Here, we show that hypothalamic PNNs are regulated by sex, gonadal hormones, and dietary interventions in a region-specific manner. Gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In some specific regions, PNNs activities are higher in females than in males; however, a high-fat diet feeding increases PNNs in this specific region in female mice but not in male mice. These results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones, and diets.

Technical Abstract: Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets.