title: Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver.
abstract: We recently described that carotid body (CB) over-activation is involved in the aetiology of insulin resistance and arterial hypertension in animal models of the metabolic syndrome. Additionally, we have demonstrated that CB activity is increased in animal models of insulin resistance, and that carotid sinus nerve (CSN) resection prevents the development of insulin resistance and arterial hypertension induced by high-energy diets. Here, we tested whether the functional abolition of CB by CSN transection would reverse pre-established insulin resistance, dyslipidaemia, obesity, autonomic dysfunction and hypertension in animal models of the metabolic syndrome. The effect of CSN resection on insulin signalling pathways and tissue-specific glucose uptake was evaluated in skeletal muscle, adipose tissue and liver.
  
  
  
  Experiments were performed in male Wistar rats submitted to two high-energy diets: a high-fat diet, representing a model of insulin resistance, hypertension and obesity, and a high-sucrose diet, representing a lean model of insulin resistance and hypertension. Half of each group was submitted to chronic bilateral resection of the CSN. Age-matched control rats were also used.
  
  
  
  CSN resection normalised systemic sympathetic nervous system activity and reversed weight gain induced by high-energy diets. It also normalised plasma glucose and insulin levels, insulin sensitivity lipid profile, arterial pressure and endothelial function by improving glucose uptake by the liver and perienteric adipose tissue.
  
  
  
  We concluded that functional abolition of CB activity restores insulin sensitivity and glucose homeostasis by positively affecting insulin signalling pathways in visceral adipose tissue and liver.
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Sacramento
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Fisiologia, Instituto Biomédico de Investigação de Luz e Imagem (IBILI), Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Facultad de Medicina. Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Salud Carlos III (ISCIII), Valladolid, España.
authors.forename: Elena
authors.initials: E
authors.lastname: Olea
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.
authors.forename: Bernardete F
authors.initials: BF
authors.lastname: Melo
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.|Unidade de Investigação em Saúde (UIS), Escola Superior de Saúde de Leiria, Instituto Politécnico de Leiria, Leiria, Portugal.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Guarino
authors.affiliation: Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Leiria, Leiria, Portugal.|Instituto de Telecomunicações, Leiria, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Fonseca-Pinto
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.
authors.forename: Cristiana R
authors.initials: CR
authors.lastname: Ferreira
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Coelho
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Facultad de Medicina. Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Salud Carlos III (ISCIII), Valladolid, España.
authors.forename: Ana
authors.initials: A
authors.lastname: Obeso
authors.affiliation: Laboratório de Fisiologia, Instituto Biomédico de Investigação de Luz e Imagem (IBILI), Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Seiça
authors.affiliation: Laboratório de Fisiologia, Instituto Biomédico de Investigação de Luz e Imagem (IBILI), Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.|Instituto Politécnico de Coimbra, Escola Superior de Tecnologia da Saúde (ESTeSC), Departmento de Ciências Complementares, Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Matafome
authors.affiliation: Centro Estudos Doenças Crónicas (CEDOC), Faculdade Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, Rua Camara Pestana, 6-6a, Edificio II, piso 3, 1150-082, Lisboa, Portugal. silvia.conde@fcm.unl.pt.
authors.forename: Sílvia V
authors.initials: SV
authors.lastname: Conde
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002344:Carotid Body / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D005947:Glucose
keywords: Adipose tissue; Carotid sinus nerve; Glucose homeostasis; Insulin sensitivity; Liver