Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats.
J C O BorgesV A B OliveiraT D A SerdanF L R SilvaC S SantosJ R B PauferroA S F RibasRichelieau ManoelA C G PereiraI S CorreaJoice Naiara Bertaglia PereiraRoberto Barbosa BazotteA C Levada-PiresTania C Pithon-CuriRenata GorjãoRui CuriSandro Massao HirabaraLaureane Nunes MasiPublished in: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (2023)
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 β3-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°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-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (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.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- resting state
- white matter
- weight loss
- blood brain barrier
- gene expression
- brain injury
- type diabetes
- transcription factor
- blood glucose
- functional connectivity
- oxidative stress
- metabolic syndrome
- adipose tissue
- lps induced
- glycemic control
- bariatric surgery
- traumatic brain injury
- computed tomography
- blood pressure
- multiple sclerosis
- cognitive impairment
- lipopolysaccharide induced
- skeletal muscle
- small molecule
- prefrontal cortex
- genome wide
- nuclear factor
- cardiovascular risk factors
- young adults
- body weight
- obese patients