The hypothalamus, one of the major regulatory centers in the brain, controls various homeostatic processes, and hypothalamic neural stem cells (htNSCs) have been observed to interfere with hypothalamic mechanisms regulating aging. NSCs play a pivotal role in the repair and regeneration of brain cells during neurodegenerative diseases and rejuvenate the brain tissue microenvironment. The hypothalamus was recently observed to be involved in neuroinflammation mediated by cellular senescence. Cellular senescence, or systemic aging, is characterized by a progressive irreversible state of cell cycle arrest that causes physiological dysregulation in the body and it is evident in many neuroinflammatory conditions, including obesity. Upregulation of neuroinflammation and oxidative stress due to senescence has the potential to alter the functioning of NSCs. Various studies have substantiated the chances of obesity inducing accelerated aging. Therefore, it is essential to explore the potential effects of htNSC dysregulation in obesity and underlying pathways to develop strategies to address obesity-induced comorbidities associated with brain aging. This review will summarize hypothalamic neurogenesis associated with obesity and prospective NSC-based regenerative therapy for the treatment of obesity-induced cardiovascular conditions.
Hypothalamus is a major regulatory center in the brain responsible for various homeostasis processes. Distinct neurons and glial cells, including microglia support the cardiovascular functions in the hypothalamus. An important cardiovascular regulatory nucleus in the hypothalamus is the Paraventricular Nucleus (PVN). Previous studies from our laboratory showed evidence for cellular senescence in the PVN. Senescence is a state of irreversible growth arrest in proliferating cells, which has been implicated in several neurodegenerative diseases. Microglia, is the resident macrophage cells of the brain that can phagocytose and initiate local inflammatory responses. Upon chronic inflammatory signaling, microglia lose its phagocytic property and enters a state of activation and proliferation. We analyzed hypothalamus from young adult mice fed with either chow (6 kcal% fat) or High Fat Diet (HFD; 60 kcal% fat) for a period of 16 weeks. Cell sorting of activated microglia using a benchtop microfluidic cell sorter revealed an increase in activated microglia in the hypothalamus after chronic HFD feeding. Microglial activation has been associated with promotion of a senescence phenotype and induction of inflammation through senescence associated secretory phenotype (SASP). To investigate this, we analyzed senescence markers in the hypothalamus. Real-time PCR revealed elevated senescent markers p53, p21 and p16, along with a significant increase (P<0.05) in SASP factors such as IL1β, MCP1 and TNFα in the HFD group compared to controls. Immunofluorescence studies confirmed the presence of senescent Iba1+ microglial cells in the PVN of HFD mice compared to their chow counterparts. Taken together, these findings suggest that senescent microglia could play a central role in the hypothalamic inflammation in HFD-induced obesity and targeting microglia will help in developing novel preventive and treatment strategy for obesity associated cardiovascular diseases. National Heart, Blood and Lung Institute grant R15HL148844; American Heart Association Institutional Research Enhancement Award – 959725. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Obesity is known to be a major factor in the increase of cardiovascular risk and inflammatory responses in the brain. It has been found that high-fat diet (HFD)-induced obesity increases sympathetic nerve activity (SNA) through a cascade of chronic metabolic processes such as an increase in oxidative stress and inflammation. The rostral ventrolateral medulla (RVLM) is a specific part of the brainstem that regulates SNA. Wheat germ (WG), a rich source of bioactive compounds including polyunsaturated fatty acid, has been shown to have an anti-inflammatory effect on the gut environment of HFD-fed mice. A healthy gut microbiota has been shown to have a regulatory effect on the gut-brain axis, especially under stress. In this study, we investigated the effects of WG supplementation on RVLM inflammation in high-fat high cholesterol diet (HFHC)-fed IL-10 KO mice. Six-week-old female C57BL/6 (WT) and IL-10 KO mice ( n = 4-5/group) were randomly assigned to treatment groups: WT and IL-10 KO fed a control diet (10% fat kcal), IL-10 KO fed HFHC (43.4% fat kcal, 1% cholesterol) diet with or without 10% WG for 12 weeks. At the end of 12 wks of treatment, animals were sacrificed and RVLM mRNA expression of proinflammatory cytokines and chemokine were analyzed using qPCR. HFHC increased the expression of IL1b, TNFa, and MCP-1 in the RVLM. WG supplementation was able to reverse the mRNA expression of IL1b (p<0.05), TNFa (p<0.05), and MCP1 (p<0.05). These results indicate that HFHC diet-induced obesity increases inflammation in the RVLM and WG supplementation could reverse these effects. Future studies would focus on understanding the mechanisms by which WG reverses the inflammation in the brain. NIH R15HL148844, AHA AIREA959725, and Oklahoma Agriculture Experiment Station 2153907 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.