Abstract
Prepubertal obesity (PPO) is now associated with early signs of renal disease. An improper eating behavior is one of the leading causes of PPO. Time restricted feeding (TRF) has been shown to be beneficial in obese patients without reducing body weight. However, the effects of TRF on renal injury during PPO have not been investigated. Therefore, the current study examined whether TRF reduces renal injury in obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats before puberty. Four-week-old SS and SSLepRmutant rats were given either ad libitum access to food for 24 hrs (control) or 8 hrs during their active phase (TRF) for 4 weeks. Body weight and food intake were significantly higher in SSLepRmutant rats versus SS rats throughout the study, and TRF did not have an impact on both parameters. Fasting blood glucose levels were similar in all groups (≤120 mg/dL). Fasting plasma insulin levels were significantly higher in SSLepRmutant rats vs SS rats (5±1 vs. 1.0±0.1 ng/mL; p<0.05), and TRF reduced fasting plasma insulin by 70% in SSLepRmutant rats. Moreover, TRF markedly improved insulin resistance in SSLepRmutant rats. At the end of the study, we did not observe any differences in MAP (via carotid catheter) among the groups. Proteinuria was significantly higher in SSLepRmutant vs SS rats (361±32 vs. 17±4 mg/day; p<0.05), and TRF only reduced proteinuria in SSLepRmutant rats (144±19 mg/day; p<0.05). We observed a significant increase in GFR (via creatinine clearance) in SSLepRmutant rats compared to SS rats (0.71±0.08 vs. 0.39±0.07 mL/min/gkwt; p<0.05), and TRF normalized GFR in SSLepRmutant rats (0.37±0.07 mL/min/gkwt; p<0.05). Glomerular injury and renal fibrosis were markedly elevated in SSLepRmutant vs SS rats, and TRF improved these histological changes. Overall, these data suggest that TRF prevents the early progression of proteinuria by possibly reducing the insulin resistant effects on GFR during PPO. NIDDK (DK109133) and AG (AG057842). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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