Time‐Restricted Feeding With High‐Fat Diet Slows Weight Gain and Reduces Renal Calcium Oxalate Crystal Formation Without Reducing Energy Intake

Renal calcium oxalate stones are closely linked to lipid metabolism disorders. A long-term high-fat diet (HFD) can lead to obesity and other metabolic disorders, which significantly contribute to stone formation. Recent studies indicate that time-restricted feeding (TRF) plays a crucial role in improving metabolic homeostasis and preventing metabolic diseases. However, its impact on kidney stone formation has yet to be investigated. We examined differences in calcium oxalate crystal formation in mouse kidneys using glyoxylic acid (Gly) modeling in HFD mouse models subjected to either ad libitum (Ad) feeding or TRF. TRF mitigated weight gain, improved blood lipid metabolism disorders, and reduced lipid deposition in the liver and kidneys, alleviating pathological damage. Compared with the Ad group, the TRF group exhibited lower urinary concentrations of oxalate and calcium ions, which corresponded with reduced expression of OPN and CD44, leading to decreased oxalate crystal formation. Gly intervention in the Ad group increased the expression of TNF-α and IL-6 in the kidneys, leading to an imbalance between oxidative stress and antioxidant responses. In contrast, TRF showed significant improvement, potentially linked to activation of the PI3K-AKT pathway. Nighttime TRF, which more closely aligns with the natural work and rest rhythms of mice, produced more pronounced effects than daytime TRF. NR1D1 expression in the kidneys was closely associated with stone formation. TRF can improve lipid metabolism and inhibit the formation of renal calcium oxalate stones, and dietary preventive strategies that align with biological rhythms demonstrate particularly significant effects.