Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice

Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment.

Feline obesity: causes, consequences and management

Regulation of food intake and body weight involves a complex balance between long-term control of fat mass involving insulin, adrenal steroids and leptin signals to the CNS and short-term, meal-related signals. Cats will normally limit their food intake to their energy requirements. However, in some instances cats appear unable to regulate energy balance. Our research has demonstrated that despite elevated circulating leptin levels in obese cats associated with increased fat mass, they continue to overeat and gain weight. This paradox of increased leptin concentrations in obesity has been observed in other species and is hypothesized to be a consequence of 'leptin resistance'.

Adjusting Body Cell Mass for Size in Women of Differing Nutritional Status

Background: Body cell mass (BCM) may be estimated in clinical practice to assess functional nutritional status, eg, in patients with anorexia nervosa. Interpretation of the data, especially in younger patients who are still growing, requires appropriate adjustment for size. Previous investigations of this general issue have addressed chemical rather than functional components of body composition and have not considered patients at the extremes of nutritional status, in whom the ability to make longitudinal comparisons is of particular importance. Objective: Our objective was to determine the power by which height should be raised to adjust BCM for height in women of differing nutritional status. Design: BCM was estimated by K-40 counting in 58 healthy women, 33 healthy female adolescents, and 75 female adolescents with anorexia nervosa. The relation between BCM and height was explored in each group by using log-log regression analysis. Results: The powers by which height should be raised to adjust BCM,A,ere 1.73. 1.73, and 2.07 in the women, healthy female adolescents, and anorexic female adolescents, respectively. A simplified version of the index, BCM/height(2), was appropriate for all 3 categories and was negligibly correlated with height. Conclusions: In normal-weight women, the relation between height and BCM is consistent with that reported previously between height and fat-free mass. Although the consistency of the relation between BCM and fat-free mass decreases with increasing weight loss, the relation between height and BCM is not significantly different between normal-weight and underweight women. The index BCM/height(2) is easy to calculate and applicable to both healthy and underweight women. This information may be helpful in interpreting body-composition data in clinical practice.

Magnetic resonance imaging analysis of the upper cervical spine extensor musculature in an asymptomatic cohort: an index of fat within muscle

AIM: To establish a simple method to quantify muscle/fat constituents in cervical muscles of asymptomatic women using magnetic resonance imaging (MRI), and to determine whether there is an age effect within a defined age range. MATERIALS AND METHODS: MRI of the upper cervical spine was performed for 42 asymptomatic women aged 18-45 years. The muscle and fat signal intensities on axial spin echo T1-weighted images were quantitatively classified by taking a ratio of the pixel intensity profiles of muscle against those of intermuscular fat for the rectus capitis posterior major and minor and inferior obliquus capitis muscles bilaterally. Inter- and intra-examiner agreement was scrutinized. RESULTS: The average relative values of fat within the upper cervical musculature compared with intermuscular fat indicated that there were only slight variations in indices between the three sets of muscles. There was no significant correlation between age and fat indices. There were significant differences for the relative fat within the muscle compared with intermuscular fat and body mass index for the right rectus capitis posterior major and right and left inferior obliquus capitis muscles (p = 0.032). Intraclass correlation coefficients for intraobserver agreement ranged from 0.94 to 0.98. Inter-rater agreement of the measurements ranged from 0.75 to 0.97. CONCLUSION: A quantitative measure of muscle/fat constituents has been developed, and results of this study indicate that relative fatty infiltration is not a feature of age in the upper cervical extensor muscles of women aged 18-45 years. (C) 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effect of body mass index changes between ages 5 and 14 on blood pressure at age 14 - Findings from a birth cohort study

Weight reduction in clinical populations of severely obese children has been shown to have beneficial effects on blood pressure, but little is known about the effect of weight gain among children in the general population. This study compares the mean blood pressure at 14 years of age with the change in overweight status between ages 5 and 14. Information from 2794 children born in Brisbane, Australia, and who were followed up since birth and had body mass index (BMI) and blood pressure measurements at ages 5 and 14 were used. Systolic and diastolic blood pressure at age 14 was the main outcomes and different patterns of change in BMI from age 5 to 14 were the main exposure. Those who changed from being overweight at age 5 to having normal BMI at age 14 had similar mean blood pressures to those who had a normal BMI at both time points: age- and sex-adjusted mean difference in systolic blood pressure 1.54 ( - 0.38, 3.45) mm Hg and in diastolic blood pressure 0.43 ( - 0.95, 1.81) mm Hg. In contrast, those who were overweight at both ages or who had a normal BMI at age 5 and were overweight at age 14 had higher blood pressure at age 14 than those who had a normal BMI at both times. These effects were independent of a range of potential confounding factors. Our findings suggest that programs that successfully result in children changing from overweight to normal-BMI status for their age may have important beneficial effects on subsequent blood pressure.

Change in lean body mass Is a major determinant of change in areal bone mineral density of the proximal femur: A 12-year observational study

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.