Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress.
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ABSTRACT:
SUBMITTER: Dalmasso C
PROVIDER: S-EPMC8516729 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: Long-term dysregulation of energy balance is the key component of the obesity epidemic. Given the harm of central obesity and the discovery that beige cells appear within white adipose tissue (WAT), enhancing the energy-expending or "browning" ability of visceral adipose tissue (VAT) has become of therapeutic interest. In this study, we focused on the regulating role of microRNA (miRNA)-27b-3p in mice epididymal white adipose tissue (eWAT) browning. Methods: High-fat diet (HFD) induced obese mice model was constructed. Expression of miR-27b-3p and Ucp1 in eWAT was measured during the course of HFD. Through tail vein injection of antimiR-27b-3p, miR-27b-3p expression was inhibited to analyze the potential role of miR-27b-3p in fat browning and metabolism. Results: miR-27b-3p was predominantly expressed in eWAT and browning ability of eWAT in HFD induced obese mice was impaired. Inhibition of miR-27b-3p enhanced browning capacity of eWAT in mice fed an HFD and led to weight loss and insulin sensitivity improvement. Conclusions: High expression of miR-27b-3p in eWAT inhibits browning ability and leads to visceral fat accumulation. It is suggested miR-27b-3p may become a potential therapeutic option for visceral obesity and its associated diseases.
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Project description:Analysis of gene expression profiles of epididymal fat from DIO rats We applied a comparative functional genomics approach to evaluate diet-induced obese (DIO) rats as an obesity model Keywords: single time point, comparison control animal vs. diet induced obese animal
2007-08-07 | GSE8700 | GEO
Project description:Background & aimsThe spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity.MethodsWe synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ signaling in mouse and human taste bud cells (TBC). In C57Bl/6 male mice, we assessed their gustatory perception and effects of their lingual application on activation of tongue-gut loop. We elucidated their effects on obesity and its related parameters in male mice fed a high-fat diet.ResultsThe two FTA, NKS-3 and NKS-5, triggered higher Ca2+ signaling than a dietary long-chain fatty acid in human and mouse TBC. Mice exhibited a gustatory attraction for these compounds. In conscious mice, the application of FTA onto the tongue papillae induced activation of tongue-gut loop, marked by the release of pancreato-bile juice into collecting duct and cholecystokinin and peptide YY into blood stream. Daily intake of NKS-3 or NKS-5 via feeding bottles decreased food intake and progressive weight gain in obese mice but not in control mice.ConclusionsOur results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.
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Project description:BackgroundAnti-inflammatory approaches are emerging as a new strategy for the treatment of depressive disorders. Ginsenoside Rb1 (GRb1), a major component of Panax ginseng, can inhibit inflammatory cascade and alleviate depressive-like behaviors. Microglia can promote or inhibit adult hippocampal neurogenesis according to their functional phenotypes. Here, we examine whether GRb1 may exert antidepressant effects by promoting a pro-neurogenic phenotype of microglia and thereby increasing neurogenesis.MethodsThe antidepressant effects of GRb1 or the licensed antidepressant imipramine (IMI) were assessed in chronic mild stress (CMS)-exposed male mice. The depressive-like behaviors of mice were evaluated by sucrose preference test, forced swimming test (FST), and tail suspension test (TST). The microglial phenotypes were identified by pro- and anti-inflammatory cytokine expression and morphological properties, analyzed by RT-qPCR, western blotting, and immunofluorescence staining. The effect of GRb1-treated microglia on adult hippocampal neurogenesis in vivo and in vitro was detected using immunofluorescence staining.ResultsBehavioral assessment indicated that GRb1 or IMI treatment alleviated depressive-like behaviors in CMS-exposed mice. Immunofluorescence examination demonstrated that GRb1 induced a pro-neurogenic phenotype of microglia via activating PPARγ in vivo and in vitro, which were effectively reversed by the PPARγ inhibitor GW9662. In addition, GRb1-treated microglia increased the proliferation and differentiation of neural precursor cells.ConclusionsThese findings demonstrated that GRb1 alleviated depressive-like behaviors of CMS-exposed male mice mainly through PPARγ-mediated microglial activation and improvement of adult hippocampus neurogenesis.
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