Obesity-Related Brain Cholinergic System Impairment in High-Fat-Diet-Fed Rats

Abstract

A link between obesity and cerebral health is receiving growing recognition. Here, we investigate in the frontal cortex and hippocampus the potential involvement of cholinergic markers in brain alterations previously reported in rats with obesity induced by diet (DIO) after long-term exposure (17 weeks) to a high-fat diet (HFD) in comparison with animals fed with a standard diet (CHOW). The obesity developed after 5 weeks of HFD. Bodyweight, systolic blood pressure, glycemia, and insulin levels were increased in DIO rats compared to the CHOW group. Measurements of malondialdehyde (MDA) provided lipid peroxidation in HFD-fed rats. Western blot and immunohistochemical techniques were performed. Our results showed a higher expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in obese rats but not the VAChT expression in the frontal cortex after 17 weeks of HFD. Furthermore, the acetylcholinesterase (AChE) enzyme was downregulated in HFD both in the frontal cortex and hippocampus. In the brain regions analyzed, it was reported a modulation of certain cholinergic receptors expressed pre- and post-synaptically (alpha7 nicotinic receptor and muscarinic receptor subtype 1). Collectively, these findings point out precise changes of cholinergic markers that can be targeted to prevent cerebral injuries related to obesity.

Anti-Inflammatory and Antioxidant Properties of Tart Cherry Consumption in the Heart of Obese Rats

“…After 17 weeks of HFD, animals were sacrificed, and heart weights were recorded. Blood parameters were reported previously as well as systolic blood pressure [26,[32][33][34][35][36]. DS and DJS groups presented a decrease in systolic blood pressure in comparison with DIO rats.…”

The M1-muscarinic acetylcholine receptor subtype may play a role in learning and memory performance in the hippocampus of neonatal monosodium glutamate-obese rats

“…Following the results carried out in DIO subjects (Silva et al ., 2019), we found that the M 1 , but not M 3 mAChR, was significantly reduced in the hippocampus of MSG-obese rats. Interestingly, the hippocampus of DIO rats had no change in the expression of M 1 , M 3 , and M 5 mAChR subtypes for 5 or 17 weeks (Martinelli et al ., 2022). On the other hand, 20-week-old obese Zucker rats only had reduced M 1 but not reduced M 3 subtype in the hippocampus (Martinelli et al ., 2021).…”

Association of Psychological distress and Physical Health with Subjective and Objective Memory in Older Adults

“…In older adults, obesity was also associated with reduced the brain’s gray matter (Beyer et al, 2019), which mediated lower memory performance (Kharabian Masouleh et al, 2016). Obesity may also lead to abnormal changes in the brain white matter (Daoust et al, 2021), cholinergic signaling system (Martinelli et al, 2022), and importantly, the hippocampal structure or functions that support memory processing (Parent et al, 2022). These effects may be caused by the low-grade inflammation, metabolic disturbances, or cerebro-microvascular impairment due to obesity (Balasubramanian et al, 2021; Buie et al, 2019; Spyridaki et al, 2016).…”