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Circadian Rhythm-Aligned Time-Restricted Feeding Prevents Ovariectomy-Induced Fat Gain, Insulin Resistance, and Osteosarcopenia in Rats
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DOI：10.1016/j.tjnut.2026.101509.png)
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Abstract
En 中文
Background: Circadian rhythm-aligned time-restricted feeding (TRF) has emerged as a non-pharmacological strategy to improve metabolic health, but its effects on estrogen-deficiency-associated disorders remain unexplored. Objectives: This study evaluated the impact of circadian rhythm-aligned TRF on metabolic and musculoskeletal health in an ovariectomy (OVX) rat model of postmenopausal estrogen deficiency. Methods: Seventy-five female Sprague-Dawley rats were used (45-OVX, 30-sham). Fifteen days after surgery, OVX rats were assigned to OVX + ad libitum (Ad lib), OVX + TRF, or OVX + liraglutide (Lira) (0.3 mg/kg/d, s.c.) groups (n = 15/group). Sham rats were assigned to sham + Ad lib or sham + TRF (n = 15/group). TRF groups had access to American Institute of Nutrition-93 maintenance (AIN-93M) rodent diet only during the dark phase (20:00-09:00), whereas Ad lib groups had 24-h access. At 4, 8, and 12 wk, glucose tolerance, fat mass, inflammatory markers, volumetric bone mineral density (vBMD), microarchitecture, oxidative stress, muscle mass, morphology, and expression of atrogin-1 and Muscle RING-finger protein-1 (MuRF-1) were assessed on subgroups of rats. Data are shown as mean +/- SEM. One-way analysis of variance with post hoc Tukey test was used (P < 0.05 significant). Results: Compared to sham + Ad lib rats, OVX + Ad lib rats had poorer glucose tolerance at 12 weeks (20.93% higher blood glucose), but OVX + TRF rats had glucose tolerance that was comparable to sham + TRF and OVX + Lira. Compared to the sham + Ad lib rats, the OVX + Ad lib rats had higher lymphocytes (62.29%) and white blood cells (WBCs) (68.35%), but these increased levels were prevented by TRF (p<0.05), with effects similar to OVX + Lira. In OVX + Ad lib rats, fat mass increased by 59.52% when compared to sham + Ad lib rats, but it remained constant in OVX + TRF rats (comparable to sham + TRF and OVX + Lira). Femoral (39.39%) and vertebral (19.10%) vBMD as well as bone stiffness (p<0.05 compared to sham + Ad lib) decreased in OVX + Ad lib rats, while bone mass and microarchitecture were maintained under TRF conditions (comparable to OVX + Lira). The levels of the skeletal muscle atrophy markers atrogin-1 and MuRF-1 were significantly greater in OVX + Ad lib rats than in sham + Ad lib rats (p<0.05), but remained constant in OVX + TRF rats (comparable to sham + TRF and OVX + Lira). Conclusions: Circadian rhythm-aligned TRF represents a lifestyle intervention that counteracts estrogen-deficiency-induced metabolic and musculoskeletal deterioration.
Keywords:
circadian rhythm
time-restricted feeding
estrogen deficiency
ovariectomy
metabolic health
osteosarcopenia
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