title: Obesity induces neuroinflammation mediated by altered expression of the renin-angiotensin system in mouse forebrain nuclei.
abstract: Obesity is a widespread health concern that is associated with an increased prevalence of hypertension and cardiovascular disease. Both obesity and hypertension have independently been associated with increased levels of inflammatory cytokines and immune cells within specific brain regions, as well as increased activity of the renin-angiotensin system (RAS). To test the hypothesis that high-fat diet (HFD) induced obesity leads to an angiotensin-II (Ang-II)-dependent increase in inflammatory cells within specific forebrain regions that are important for cardiovascular regulation, we first assessed microglial activation, astrocyte activation, inflammation and RAS component gene expression within selected metabolic and cardiovascular control centers of the forebrain in adult male C57BL/6 mice given either a HFD or a low-fat diet (LFD) for 8weeks. Subsequently, we assessed the necessity of the paraventricular nucleus of the hypothalamus (PVN) angiotensin type-1a (AT1a) receptor for these responses by using the Cre/lox system in mice to selectively delete the AT1a receptor from the PVN. These studies reveal that in addition to the arcuate nucleus of the hypothalamus (ARC), the PVN and the subfornical organ (SFO), two brain regions that are known to regulate blood pressure and energy balance, also initiate proinflammatory responses after the consumption of a diet high in fat. They further indicate that some, but not all, of these responses are reversed upon deletion of AT1a specifically within the PVN.
authors: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, United States. Electronic address: adekloet@ufl.edu.
authors: Annette D
authors: AD
authors: de Kloet
authors: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, United States.
authors: David J
authors: DJ
authors: Pioquinto
authors: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors: Dan
authors: D
authors: Nguyen
authors: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors: Lei
authors: L
authors: Wang
authors: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors: Justin A
authors: JA
authors: Smith
authors: Department of Pharmacodynamics, College of Pharmacy, University of Florida, United States.
authors: Helmut
authors: H
authors: Hiller
authors: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, United States.
authors: Colin
authors: C
authors: Sumners
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015992:Body Mass Index; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000150:complications*; D016548:Prosencephalon / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics
chemical_list: D000804:Angiotensin II; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012097:Repressor Proteins; C491049:Aif1 protein, mouse; C101750:Sim1 protein, mouse; C560425:Vasn protein, mouse
keywords: Angiotensin type-1 receptor; Astrocyte; High-fat diet; Microglia; Paraventricular nucleus