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Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

ABSTRACT: Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals' intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression.

SUBMITTER: Joshi RN

PROVIDER: S-EPMC3772180 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

Joshi R N RN Safadi F F FF Barbe M F MF Del Carpio-Cano Fe F Popoff S N SN Yingling V R VR

Bone 20110723 4

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the ...[more]

PMID: 21807131

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Project description:UnlabelledThere is a debate over the independent effects of aerobic fitness and body fatness on mortality and disease risks.PurposeTo determine whether a 25% energy deficit that produces equal change in body fatness leads to greater cardiometabolic benefits when aerobic exercise is included.MethodsThirty-six overweight participants (16 males/20 females) (39 +/- 1 yr; 82 +/- 2 kg; body mass index = 27.8 +/- 0.3 kg x m2, mean +/- SEM) were randomized to one of three groups (n = 12 for each) for a 6-month intervention: control (CO, weight-maintenance diet), caloric restriction (CR, 25% reduction in energy intake), or caloric restriction plus aerobic exercise (CR + EX, 12.5% reduction in energy intake plus 12.5% increase in exercise energy expenditure). Food was provided during weeks 1-12 and 22-24. Changes in fat mass, visceral fat, VO2peak (graded treadmill test), muscular strength (isokinetic knee extension/flexion), blood lipids, blood pressure, and insulin sensitivity/secretion were compared.ResultsAs expected, VO2peak was significantly improved after 6 months of intervention in CR + EX only (22 +/- 5% vs 7 +/- 5% in CR and -5 +/- 3% in CO), whereas isokinetic muscular strength did not change. There was no difference in the losses of weight, fat mass, or visceral fat and changes in systolic blood pressure (BP) between the intervention groups. However, only CR + EX had a significant decrease in diastolic BP (-5 +/- 3% vs -2 +/- 2% in CR and -1 +/- 2% in CO), in low-density lipoprotein (LDL) cholesterol (-13 +/- 4% vs -6 +/- 3% in CR and 2 +/- 4% in CO), and a significant increase in insulin sensitivity (66 +/- 22% vs 40 +/- 20% in CR and 1 +/- 11% in CO).ConclusionsDespite similar effect on fat losses, combining CR with exercise increased aerobic fitness in parallel with improved insulin sensitivity, LDL cholesterol, and diastolic BP. The results lend support for inclusion of an exercise component in weight loss programs to improve metabolic fitness.

Project description:ObjectivesCaloric restriction (CR) has been shown to slow the aging processes in a number of preclinical studies and reduces expression of aging-associated biomarkers in human trials. We hypothesized that CR would lead to increased incidence of ketosis and that ketosis in CR individuals would alter the aging-protective effects of CR or biomarkers thereof.Design/setting/participantsWe analyzed data from the "Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE, Phase 2)" Public Use Database available at calerie.duke.edu. In this study, non-obese adults between the ages of 21 and 50 were randomized to 25% CR or control (ad lib) diet groups and extensively monitored for two years. Given our focus on the effect of caloric restriction on ketosis, individuals with detectible ketones during the baseline visit (pre-randomization) and those with missing data for ketone testing were excluded from the analysis, leaving 71 control and 117 CR participants.MeasurementsWe analyzed the incidence of ketosis as well as ketosis free survival in control and CR participants and assessed the effect of ketosis on a number of clinical lab values, functional assessments, and participant survey data related to aging biology.ResultsWe report that CR was associated with modestly increased incidence of ketosis (4.4% in CR vs 1.9% in control), though CR-associated changes in T3, VO2, SUMPT-WT (weight normalized composite strength score - peak torque), physical functioning, and general health did not appear to be altered by the presence or absence of ketosis. Additional observations of interest include: 1) striking patterns of biomarker expression changes (MCP-1, TNFα, TGF-β1, GH) in both the control and CR participants between the baseline visit and the 24-month post-randomization visit and 2) pro-growth/anti-inflammatory baseline (pre-randomization) biomarker expression profile in CR individuals that later test ketone positive relative to other CR individuals.ConclusionsCR modestly increases the incidence of ketosis in healthy adults, yet the increase in ketosis in CR patients did not significantly affect the aging-protective effects of CR. However, given the relatively small number of participants who were ketone positive, further investigation in larger study cohorts is still required for definitive conclusions.

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Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

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Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

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