Abstract
BackgroundIn the current study, our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets (high-fat, high-protein, low-calorie, high-protein and low-calorie).MethodsRats were treated with high-fat, high-protein, low-calorie, low-calorie high-protein diets for 10 weeks and then behavioral and molecular assessments were evaluated.ResultsStatistical analysis showed the percentage of open arm time was increased in the high-protein, low-calorie and low-calorie high-protein groups compared with old control (old-C) rats. The percentage of open arm entries was increased in the low-calorie and low-calorie high-protein group compared with old-C rats. The body weight and serum triglyceride were decreased in the low-calorie and low-calorie high-protein groups in comparison to control old rats. Low-calorie and low-calorie high-protein treatments statistically enhanced caspase-3 level compared with old-C rats in the hippocampus and prefrontal cortex. Treatment of old rats with high-protein, low-calorie and low-calorie high-protein could increase Klotho-α level compared with control old rats. The levels of Klotho-α, c-fos and brain-derived neurotrophic factors were decreased in the low-calorie high-protein group in Klotho inhibitor's presence compared with the low-calorie high-protein group.ConclusionAccording to our findings, Klotho-α level was reduced in old rats. Low-calorie, high-protein and particularly low-calorie high-protein diets increased this protein level and consequently increased neuronal plasticity and improved memory function.Graphic abstract
Highlights
In the current study, our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets
All rats in each group were housed individually (n = 7): (1) adult control, adult rats were treated with control diet for 10 weeks, (2) old control, old rats were treated with control diet for 10 weeks, (3) high-fat diet, old rats were treated with high fat food for 10 weeks, (4) high-protein diet, old rats were treated with high-protein food for 10 weeks, (5) low-calorie diet, old rats were treated with low amount of control diet for 10 weeks, (6) low-calorie high-protein diet, old rats were treated with low amount of high-protein food for 10 weeks
In the second experimental design, 20-month-old male rats were randomly put in four groups. (1) old control, old rats were treated with control diet for 10 weeks, (2) low-calorie high-protein diet, old rats were treated with low amount of high-protein food for 10 weeks, (3) old-C and d-saccharic acid 1,4-lacton diet, old rats were treated with low amount of high-protein food for 10 weeks and received d-saccharic acid 1,4-lactone twice per week for 10 weeks, (4) low-calorie diet and d-saccharic acid 1,4-lacton diet, old rats were treated with low amount of high-protein food for 10 weeks and received d-saccharic acid 1,4-lactone twice per week for 10 weeks
Summary
Our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets (high-fat, high-protein, low-calorie, high-protein and low-calorie). Klotho is an obligate co-receptor of fibroblast growth factor (FGF) receptors (FGFRs) and Klotho/FGFRs complex act many metabolic functions in many tissues such as the kidney, heart and brain [7]. Studies have detected the downstream signaling proteins of Klotho in different pathogenic contexts; for example, it has been shown that a high-protein diet could amend fibroblast growth factor 21 (FGF21) expression in the brain, and subsequently controls dietary intake and initiates Klotho gene expression in the neurons, and induces neuroprotective effect against brain injury [8, 9]. Fibroblast growth factor 23 (FGF23) is a known co-receptor of Klotho in the kidney, and recently, it has been demonstrated that FGF23/ Klotho complex could enhance synaptic density in the hippocampal neurons [10]
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