PMID- 37377307 OWN - NLM STAT- MEDLINE DCOM- 20230629 LR - 20230629 IS - 1414-431X (Electronic) IS - 0100-879X (Linking) VI - 56 DP - 2023 TI - Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats. PG - e12742 LID - S0100-879X2023000100640 [pii] LID - 10.1590/1414-431X2023e12742 [doi] AB - Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective beta3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80 degrees C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1beta, and IL-6 gene expression and IL-1beta and the subunit of the transcription factor NF-kappaB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area. FAU - Borges, J C O AU - Borges JCO AUID- ORCID: 0000-0002-0196-0156 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Oliveira, V A B AU - Oliveira VAB AUID- ORCID: 0000-0002-9352-6735 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Serdan, T D A AU - Serdan TDA AUID- ORCID: 0000-0002-1977-0529 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Silva, F L R AU - Silva FLR AUID- ORCID: 0000-0002-8917-4618 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Santos, C S AU - Santos CS AUID- ORCID: 0000-0002-5631-440X AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Pauferro, J R B AU - Pauferro JRB AUID- ORCID: 0000-0001-5973-8008 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Ribas, A S F AU - Ribas ASF AUID- ORCID: 0000-0002-2189-9735 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Manoel, R AU - Manoel R AUID- ORCID: 0000-0002-2433-2873 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Pereira, A C G AU - Pereira ACG AUID- ORCID: 0000-0002-4338-9138 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Correa, I S AU - Correa IS AUID- ORCID: 0000-0001-9325-8067 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Pereira, J N B AU - Pereira JNB AUID- ORCID: 0000-0003-2609-5450 AD - Secao de Producao de Imunobiologicos, Bioindustrial Centro, Instituto Butantan, Sao Paulo, SP, Brasil. FAU - Bazotte, R B AU - Bazotte RB AUID- ORCID: 0000-0001-8563-7913 AD - Programa de Pos-Graduacao em Ciencias Farmaceuticas, Departamento de Farmacologia e Terapeutica, Universidade Estadual de Maringa, Maringa, PR, Brasil. FAU - Levada-Pires, A C AU - Levada-Pires AC AUID- ORCID: 0000-0002-5320-5953 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Pithon-Curi, T C AU - Pithon-Curi TC AUID- ORCID: 0000-0002-9714-9105 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Gorjao, R AU - Gorjao R AUID- ORCID: 0000-0002-9655-1477 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Curi, R AU - Curi R AUID- ORCID: 0000-0001-5095-9154 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. AD - Secao de Producao de Imunobiologicos, Bioindustrial Centro, Instituto Butantan, Sao Paulo, SP, Brasil. FAU - Hirabara, S M AU - Hirabara SM AUID- ORCID: 0000-0002-7392-0444 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. FAU - Masi, L N AU - Masi LN AUID- ORCID: 0000-0001-9472-7304 AD - Programa Interdisciplinar de Ciencias da Saude, Universidade Cruzeiro do Sul, Sao Paulo, SP, Brasil. AD - Departamento de Ciencias Fisiologicas, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC, Brasil. LA - eng PT - Journal Article DEP - 20230626 PL - Brazil TA - Braz J Med Biol Res JT - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas JID - 8112917 RN - IY9XDZ35W2 (Glucose) RN - 0 (Leptin) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Rats MH - Animals MH - *Glucose/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - Rats, Wistar MH - Leptin MH - Blood Glucose/metabolism MH - Neuroinflammatory Diseases MH - Brain/metabolism MH - Obesity MH - Hippocampus/metabolism MH - Inflammation MH - Insulin EDAT- 2023/06/28 13:09 MHDA- 2023/06/29 06:42 CRDT- 2023/06/28 08:16 PHST- 2023/04/10 00:00 [received] PHST- 2023/05/05 00:00 [accepted] PHST- 2023/06/29 06:42 [medline] PHST- 2023/06/28 13:09 [pubmed] PHST- 2023/06/28 08:16 [entrez] AID - S0100-879X2023000100640 [pii] AID - 10.1590/1414-431X2023e12742 [doi] PST - epublish SO - Braz J Med Biol Res. 2023 Jun 26;56:e12742. doi: 10.1590/1414-431X2023e12742. eCollection 2023.