Determinants of bone density in 30- to 65-year-old women: A co-twin study

Introduction: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent.

Methods: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants.

Results: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 ± 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass.

Conclusion: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.

Impaired activation of AMP-Kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics

Adiponectin is an adipocyte-derived hormone associated with antidiabetic actions. In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2. In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects. Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052). In lean myotubes, gAD activates AMPK[alpha]1 and -[alpha]2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACC[beta]) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside. In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 [mu]g/ml) was blunted, but higher concentrations (0.5 [mu]g/ml) stimulated AMPK[alpha]1 and -[alpha]2 activities, AMPK and ACC[beta] phosphorylation, and fatty acid oxidation. In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPK[alpha]1 activity and AMPK phosphorylation; however, ACC[beta] phosphorylation and fatty acid oxidation were unaffected. Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPK[alpha] and ACC[beta] or the expression and activity of the upstream AMPK kinase, LKB1. These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.

Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

The role of ethnicity and culture in body image and disordered eating among males

An increasing number of researchers have examined body image concerns, disordered eating, and other behaviors associated with increasing muscle size among men from different cultural groups. However, to date there has been no synthesis or evaluation of these studies. In this paper we specifically review studies which have included a comparison between males from different cultural groups with White males on body image concerns or other related behaviors. The groups include Blacks, Hispanic Americans, Asians, Native Americans, Pacific Islanders, and men from Middle Eastern countries. Overall, evidence suggests that males from a range of cultural groups engage in more extreme body change strategies and binge eating than Whites. On the other hand, there is no consistent pattern which summarizes the nature of body image concerns across the different cultures. Mediating and/or moderating variables are proposed to account for the inconsistent findings. These include body build, levels of acculturation, socio-economic status, media exposure, and internalization of the muscular and lean body ideal.

Effects of cannabinoid receptors on skeletal muscle oxidative pathways

The endocannabinoids, a recently discovered endogenous, lipid derived, signaling system regulating energy metabolism, have effects on central and peripheral energy metabolism predominantly via the cannabinoid receptor type 1 (CB1). CB1 is expressed centrally in the hypothalamus and nucleus accumbens and peripherally in adipocytes and skeletal muscle. This study determined the effect of endocannabinoids on the expression of genes regulating energy metabolism in human skeletal muscle. Primary cultures of myotubes (lean and obese; n = 3/group) were treated with the cannabinoid receptor agonist, anandamide (AEA) (0.2 and 5 μM) and the CB1 specific antagonist AM251 (0.2 and 5 μM) separately and in combination for 24 h. The expression of mRNA for AMP-activated protein kinase (AMPK) alpha 1 (α1) and alpha 2 (α2), pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) were determined using ‘Real Time’ RT-PCR. AMPKα1 mRNA increased in lean and obese myotubes in response to AM251 (P < 0.05). AEA inhibited the effect of AM251 on AMPKα1 mRNA levels in myotubes from lean and obese subjects (P < 0.05); the dose–response curve was shifted to the left in the obese. In response to AM251, irrespective of the presence of AEA, PDK4 expression was decreased in lean and obese myotubes (P < 0.05). Taken together these data suggest that endocannabinoids regulate pathways affecting skeletal muscle oxidation, effects particularly evident in myotubes from obese individuals.

Leptin stimulation of COXIV is impaired in obese skeletal muscle myotubes

Objective
To investigate the effects of leptin on the mRNA abundance of key genes involved in fatty acid oxidation and mitochondrial biogenesis in cultured skeletal muscle myotubes derived from lean and obese individuals.

Research methods and procedures
Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Two distinct primary cell culture groups were established (Lean and Obese) n = 7 in each group. Differentiated cultures were then exposed to leptin (2.5 μg/ml) for 6 h. mRNA expression was subsequently measured by real-time PCR analysis.

Results
Basal mRNA expression of βHAD, COXIII, COXIV, PGC-1α and SOCS3 in the cultured human skeletal muscle myotubes were similar, however, PDK4 mRNA was elevated (P < 0.05) in the myotubes derived from obese individuals. The addition of leptin resulted in a 2.5-fold increase in COXIV mRNA expression in the myotubes derived from Lean individuals only (P < 0.05). There was also a tendency for leptin to increase COXIII, βHAD and PDK4 mRNA expression in this same group. Leptin had no impact on the gene expression of all measured transcripts in myotubes derived from obese individuals.

Conclusion
Short-term exposure of human skeletal muscle myotubes to leptin stimulated the expression of the mitochondrial enzyme COXIV in myotubes derived from lean individuals, an effect that was abrogated in myotubes derived from obese individuals. These data demonstrate a novel capacity for leptin to increase mitochondrial biogenesis and thus, a possible increased capacity for lipid oxidation and the persistence of a defect in leptin signalling in human myotubes cultured from obese individuals.

Changes in weight and waist circumference over 9 years in a Scottish population

Objective: To document patterns of measured weight and waist circumference (WC) change and the increase in overweight and obesity over a 9-year period. Subjects/Methods: A total of 1044 subjects from two age-defined cohorts aged 39 and 59 in 1991. Height, weight and WC were measured in 1991, 1995 and 2000 and body mass index (BMI) was calculated. Pattern of weight and WC change was studied over approximately 9 years. Results: The prevalence of overweight and obesity increased markedly and the younger cohort showed greater increases in weight and WC than the older cohort. There was no significant difference in mean BMI and/or mean 9-year weight change between men and women in either age cohort, and mean weight gain was similar for all occupational groups. Only 20% of subjects maintained a stable weight (plusminus2 kg), while 42.2 and 17.6% gained greater than 5 and 10 kg over the 9-year period, respectively. The rate of weight gain appeared to be relatively steady over the 9 years among younger subjects but declined in the older subjects in the second half of the observation period. Conclusions: Health promotion strategies to prevent weight gain need to be population-based, targeting all social and age groups, but particularly those in their early middle-age.

Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26 year old female twins

Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2–6) with an average of 1.8 years between measurements (range 0.7–6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the “linear growth” period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E. 0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the “post-linear growth” period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p<0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p<0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.

Benefits of a year-long workplace weight loss program on cardiovascular risk factors

Objective: To assess the effectiveness of a year-long workplace weight loss program in reducing risk factors of coronary heart disease.

Design: A randomised, controlled study of low fat (25% of dietary energy) diet- and/or moderate exercise-induced weight loss interventions in free-living, middle-aged men. Compliance was monitored from food and activity diaries at monthly blood pressure measurement sessions. Blood was sampled and body composition determined from dual energy X-ray absorptiometry before and after 12 months.

Subjects and setting: Fifty-eight overweight men (mean [+ or -] SD age: 43.4 [+ or -] 5.7 years; BMI 29.0 [+ or -] 2.6 kg/[m.sup.2]), recruited from a national corporation, were instructed into diet (n = 18) exercise (a 21) or control (n = 19) groups over 12 months; 16 control subjects combined diet and exercise (n = 16) for the subsequent 12 months.

Main outcome measures: At 12 months, weight, total and regional fat and lean mass, dietary energy and percentage dietary fat intake, physical activity indices, systolic and diastolic blood pressure, serum insulin, blood lipids and lipoproteins.

Statistical analyses: Differences between groups were tested using analysis of variance with Scheffe post hoc test. Differences between pre- and post-intervention variables were tested using Students' paired t-tests. Pearson's correlation coefficient and univariate linear regression identified association between dependent variables, multiple stepwise regression identified specific predictors.

Results: Weight loss with either diet or exercise resulted in a reduction in systolic blood pressure (-3.3 [+ or -] 1.7%), diastolic blood pressure (-4.8 [+ or -] 1.3%) and LDL cholesterol (-3.9 [+ or -] 2.8%), a rise in HDL cholesterol (+10.0 [+ or -] 3.8%) and a change in the LDL/HDL ratio (-8.9 [+ or -] 3.5%). Abdominal fat loss (-26.8 [+ or -] 3.6% after diet; -16.6 [+ or -] 4.5% after exercise; -21.0 [+ or -] 4.7% after diet and exercise) was the strongest predictor of change in blood pressure: twenty percent abdominal fat loss predicted a percentage fall of 2.4 [+ or -] 0.05% in systolic blood pressure and 5.4 [+ or -] 0.07% in diastolic blood pressure. Greater abdominal fat loss was associated with the greatest decrease in serum insulin (P < 0.05).

Conclusion: Modest changes in diet and exercise effected by a low cost workplace-based education program achieved weight loss, loss of abdominal fat, reduced blood pressure and serum insulin and improved blood lipid concentrations. (Nutr Diet 2002;59:87-96)

Conjugated linoleic acid decreases fat accretion in pigs evaluation by dual-energy X-ray absorptiometry

Thirty female Large White × Landrace pigs (average weight 57·2 (SD 1·9) kg) were allocated to one of six dietary treatments containing 0, 1·25, 2·5, 5·0, 7·5 or 10·0 g 55 % conjugated linoleic acids (CLA) isomers (CLA-55)/kg diet and fed for 8 weeks. Each pig was scanned at 0, 28 and 56 d and again at post slaughter using dual-energy X-ray absorptiometry (DXA) to determine the temporal pattern of body composition responses. Values determined by DXA were adjusted using regression equations generated from validation experiments between chemically and DXA-predicted values. Overall, there was a significant linear reduction in fat content with the increasing levels of CLA in the diet (P=0·007, P=0·011, P=0·008 at week 4, week 8 and for the carcass, respectively). The greatest improvement was recorded at the early stages of CLA supplementation and for the highest dose of CLA (week 4, -19·2 % compared with week 8, -13·7 %). In the first 4 weeks of feeding CLA, pigs receiving 10 g CLA-55/kg diet deposited 93 g less fat/d than pigs fed basal diets (P=0·002) compared with only 6 g less fat than control animals in the final 4 weeks. Lean content and lean deposition rate were maximised at 5 and 2·5 g CLA-55/kg diet for the first 4 weeks (P=0·016) and the final 4 weeks of treatment (P=0·17), respectively. DXA estimates of bone mineral content and bone mineral density were not affected by CLA supplementation throughout the experiment. These data demonstrate that dietary CLA decreases body fat in a dose-dependent manner and that the response is greatest over the initial 4 weeks of treatment.

Genetic variation in BEACON influences quantitative variation in metabolic syndrome-related phenotypes

The BEACON gene (also known as UBL5) was identified as differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity, type 2 diabetes, and dyslipidemia. The human homologue of BEACON is located on chromosome 19p, a region likely to contain genes affecting metabolic syndrome–related quantitative traits as established by linkage studies. To assess whether the human BEACON gene may be involved in influencing these traits, we exhaustively analyzed the complete gene for genetic variation in 40 unrelated individuals and identified four variants (three novel). The two more common variants were tested for association with a number of quantitative metabolic syndrome–related traits in two large cohorts of unrelated individuals. Significant associations were found between these variants and fat mass (P = 0.026), percentage of fat (P = 0.001), and waist-to-hip ratio (P = 0.031). The same variants were also associated with total cholesterol (P = 0.024), LDL cholesterol (P = 0.019), triglycerides (P = 0.006), and postglucose load insulin levels (P = 0.018). Multivariate analysis of these correlated phenotypes also yielded a highly significant association (P = 0.0004), suggesting that BEACON may influence phenotypic variation in metabolic syndrome–related traits.

Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes

OBJECTIVE—To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training.

RESEARCH DESIGN AND METHODS—We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60–80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA_1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months.

RESULTS—Compared with the WL group, HbA_1c decreased significantly more in the RT&WL group (–0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&WL group compared with the WL group (0.9 kg, P < 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months (P < 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months.

CONCLUSIONS—In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.

Pursuit of the muscular ideal: Physical and psychological consequences and putative risk factors

Developing a lean muscular figure for the purposes of sports and/or appearance has become a central issue for males. Concern has been raised because the desire to develop such a body build may lead to the adoption of numerous health-threatening behaviors. Consequently, this review presents a comprehensive analysis of the physical and psychological consequences that result from the use of steroids (legal and illegal), ephedrine, and deleterious dieting strategies specific to males. Putative risk factors for these behaviors will be identified, and the clinical disorder associated with the extreme abuse of these behaviors, muscle dysmorphia, will be examined.

Dietary conjugated linoleic acid improves carcass leanness without altering meat quality in the growing pig

One constraint facing the pig industry is that ad libitum feeding can often result in high levels of body fat and technologies which can reduce the ratio of lean to fat deposition in the pig are continually being explored. Conjugated linoleic acids have been shown to decrease body fat content in pigs. Therefore, the aim of this study was to determine whether dietary conjugated linoleic acids supplementation has any effect on meat quality and carcass characteristics in finisher pigs. Sixty female crossbred (Large White × Landrace) pigs (average initial weight 56.6 ± 1.9 kg and average initial P2 backfat 11.4 ± 1.3 mm) were used in the present study. Pigs were individually housed and randomly allocated to 1 of 6 dietary treatments: 0, 0.125, 0.25, 0.50, 0.75 or 1.0% (w/w) of conjugated linoleic acids-55. The wheat-based diets were formulated to contain 14.3 MJ DE and 9.3 g available lysine per kg and were fed ad libitum for 8 weeks. Pigs were slaughtered and meat quality was determined on the longissimus thoracis using standard techniques. Dietary conjugated linoleic acids reduced subcutaneous back fat in a linear manner with effects being most pronounced in the middle back fat layer. There was also a linear (P<0.001) decrease in intramuscular fat with increasing dietary conjugated linoleic acids supplementation. However, there was no effect of conjugated linoleic acids on subjective measures of marbling of the loin. Also, loin muscle ultimate pH (P = 0.94), lightness values (P = 0.46) subjective colour scores (P = 0.79), cooking loss (P = 0.71), drip loss (P = 0.40), shear force (P = 0.61) and subjective measures of wetness/firmness (P = 0.19) were unaffected. Dietary conjugated linoleic acids did not alter oxidation, as measured by the level of TBARs at day 1 post-slaughter (P = 0.38) or after 9 days of simulated retail display (P = 0.35). These data confirm that dietary conjugated linoleic acids can improve carcass quality by decreasing back fat depths without having any detrimental effects on meat quality.

The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-Kinase in cultured skeletal muscle of obese humans

Context: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents.

Objective: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans.

Results: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-ß Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 (~3.5-fold) and SOCS3 mRNA (~2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-ß-D-ribofuranoside) activation of AMPK signaling.

Conclusions: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.