title: Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice.
abstract: Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.
authors.affiliation: Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil.|Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Leandro Ceotto Freitas
authors.initials: LCF
authors.lastname: Lima
authors.affiliation: Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Soraya Wilke
authors.initials: SW
authors.lastname: Saliba
authors.affiliation: Health Science Post-graduate Program, UNIMONTES, Montes Claros, MG, Brazil.
authors.forename: João Marcus Oliveira
authors.initials: JMO
authors.lastname: Andrade
authors.affiliation: Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Puebla
authors.initials: P
authors.lastname: Cassini-Vieira
authors.affiliation: Texas Tech University, Lubbock, TX, USA.
authors.forename: John David
authors.initials: JD
authors.lastname: Feltenberger
authors.affiliation: Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Lucíola Silva
authors.initials: LS
authors.lastname: Barcelos
authors.affiliation: Health Science Post-graduate Program, UNIMONTES, Montes Claros, MG, Brazil.
authors.forename: André Luiz Sena
authors.initials: ALS
authors.lastname: Guimarães
authors.affiliation: Health Science Post-graduate Program, UNIMONTES, Montes Claros, MG, Brazil.
authors.forename: Alfredo Mauricio Batista
authors.initials: AMB
authors.lastname: de-Paula
authors.affiliation: Department of Pharmacology and Department of Physiology - ICB, Universidade Federal de Minas Gerais (UFMG), Avenida Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Antônio Carlos Pinheiro
authors.initials: ACP
authors.lastname: de Oliveira
authors.affiliation: Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil. sergiosousas@hotmail.com.|Health Science Post-graduate Program, UNIMONTES, Montes Claros, MG, Brazil. sergiosousas@hotmail.com.
authors.forename: Sérgio Henrique Sousa
authors.initials: SHS
authors.lastname: Santos
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D059305:Diet, High-Fat; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects; D008820:Mice, Obese; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology; D045442:Rotarod Performance Test; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D056564:Sirtuin 1; D017378:Quinolinic Acid
keywords: Huntington’s disease; Metabolic syndrome; Quinolinic acid; Sirtuin