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.
OBJECTIVE: This study evaluated the impact of TRF on metabolic and musculoskeletal health in an ovariectomy(OVX) rat model of postmenopausal estrogen deficiency.
METHODS: Seventy-five female Sprague-Dawley(SD) rats were used (45-OVX, 30-sham). Fifteen days post-surgery, OVX rats were assigned to OVX + ad libitum(Ad lib), OVX + TRF, or OVX + liraglutide(Lira)(0.3 mg/kg/day, 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 AIN-93M rodent diet only during the dark phase(8:00 PM-9:00 AM), while Ad lib groups had 24-hour access. At 4, 8, and 12 weeks, glucose tolerance, fat mass, inflammatory markers, bone mineral density(BMD), 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 ANOVA with post-hoc Tukey test was used(p<0.05 significant).
RESULTS: At 12-weeks, OVX + Ad lib rats showed impaired glucose tolerance (17.31% higher blood glucose vs. sham + Ad lib), whereas OVX + TRF rats exhibited improved glucose clearance (26.09%). OVX + Ad lib rats demonstrated increased white blood cells(WBCs) (40.60%) and lymphocytes (38.38%) at 12-weeks; TRF prevented these elevations(p<0.05). Fat mass increased by 37.31% in OVX + Ad lib rats but remained unchanged in OVX + TRF rats. At 12-weeks, OVX + Ad lib rats showed decrease in femoral (64.99%) and vertebral (23.61%) BMD, and reduced bone stiffness(p<0.05), while TRF preserved bone mass and microarchitecture. Muscle atrophy markers(atrogin-1 and MuRF-1) increased by ∼94% in OVX + Ad lib rats but were unchanged with TRF.
CONCLUSIONS: TRF represents a lifestyle intervention that counteracts estrogen deficiency-induced metabolic and musculoskeletal deterioration.
