Relative Lean Mass Research Articles

Macrophage TNF-α contributes to insulin resistance and hepatic steatosis in diet-induced obesity

Obesity is commonly associated with development of insulin resistance and systemic evidence of inflammation. Macrophages contribute to inflammatory amplification in obesity and may contribute directly to insulin resistance and the development of nonalcoholic fatty liver disease through the production of inflammatory cytokines, including tumor necrosis factor (TNF)-alpha. To test this hypothesis, we transplanted male wild-type (WT) and TNF-alpha deficient (KO) mice with either TNF-alpha-sufficient (TNF-alpha(+/+)) or TNF-alpha-deficient (TNF-alpha(-/-)) bone marrow. After consuming a high-fat diet for 26 wk, metabolic and morphometric characteristics of the animals were analyzed. While there were no differences in terms of relative weight gain, body composition analysis yielded a lower relative adipose and higher relative lean mass in mice lacking TNF-alpha, which was partially explained by reduced epididymal fat pad and liver weight. TNF-alpha(-/-) -->KO mice exhibited enhanced insulin sensitivity compared with that observed in TNF-alpha(+/+)-->KO mice; remarkably, no protection against insulin resistance was provided by transplanting TNF-alpha(-/-) bone marrow in WT mice compared with TNF-alpha(+/+)-->WT. The preserved insulin sensitivity seen in TNF-alpha(-/-)-->KO mice provided protection against the development of hepatic steatosis. Taken together, these data indicate that macrophage-derived TNF-alpha contributes to the pattern and extent of fat accumulation and insulin resistance in diet-induced obesity; however, this contribution is negligible in the presence of host-derived TNF-alpha.

The relative power output and relative lean body mass of World and Olympic male and female champions with implications for gender equity

A uniform measure of the gender-related differential performance of female and male Olympic and World champions is proposed: relative power output applied to the environment. Laws of physics are employed to derive equations for estimating relative power output. In previous controlled laboratory studies, equally trained male and female athletes were shown to have a relative power output not significantly different from relative lean body mass. As to the estimated power output for 32 Olympic and World championship events contested between 1976 and 2004, eight in running, four in speed skating, three in jumping, twelve in swimming and five in rowing: 100% of the 32 event mean percentage differences in power output and 96% of the 411 event percentage differences in power output are within one standard deviation of the appropriate lean body mass percentage difference, consistent with equality of training. For 1952 – 1972, significantly higher percentage differences in power output are estimated in running and swimming compared with 1976 – 2004, consistent with women being less well trained than men during that earlier period. It is noted that efforts in recent years to provide equality of opportunity for female athletes coincide with equalization of estimated relative power output in competition with the relative lean body mass.

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Although the majority of children with isolated growth hormone (GH) deficiency have a good growth response to GH-releasing hormone (GHRH), the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that, in mice with GHRH gene ablation (GHRH knockout; GHRHKO), even twice-daily injections of a GHRH analog are unable to normalize growth. CJC-1295 is a synthetic GHRH analog that selectively and covalently binds to endogenous albumin after injection, thereby extending its half-life and duration of action. We report the effects of CJC-1295 administration in GHRHKO animals. Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 microg of CJC-1295 at intervals of 24, 48, and 72 h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48 and 72 h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24 and 48 h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once-daily administration of CJC-1295 is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48 or 72 h.

Bed rest and myopathies

The loss of skeletal muscle with injury or critical illness can be dramatic. This review emphasizes the importance of skeletal muscle as a metabolic reserve. Changes in protein metabolism with bed rest alone and during physiological stress are discussed. Nutritional and hormonal interventions that ameliorate the loss of skeletal muscle are highlighted. The loss of skeletal muscle that occurs with inactivity alone can be prevented by nutritional supplementation with an essential amino acid formula. Bed rest with accompanying hypercortisolemia produces a threefold greater loss of skeletal muscle than bed rest alone. Essential amino acids stimulate muscle anabolism during acute hypercortisolemia; however, their effects during chronic hypercortisolemia must be explored. Skeletal muscle loss with trauma or critical illness is due in great part to the interaction of bed rest (muscular inactivity) and stress (hypercortisolemia). Younger individuals respond to nutritional and pharmacological interventions during bed rest alone. Given a lower relative lean mass in the elderly and the importance of skeletal muscle as a metabolic reserve during stress, it is understandable that clinical outcomes are worse in older patients. Countermeasures to the loss of skeletal muscle, especially in the stressed patient, must be developed.

Antipsychotic drug-induced weight gain: development of an animal model

Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

Effect of significant intermediate-term weight loss on serum leptin levels and body composition in severely obese subjects.

Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery. Obese subjects (body mass index [BMI] >35 kg/m2, n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison. SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001). SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.

Aging and the neuroendocrine regulation of reproduction and body weight.

Aging in men is associated with a decline in trophic factors such as testosterone (T), alterations in body composition and impaired energy and body weight regulation. We performed studies to investigate the mechanisms underlying age-related changes in the neuroendocrine control of testis function, body composition, food intake and body weight in the Brown Norway (BN) rat. We found that similar to aging men, male BN rats demonstrate both primary and secondary testicular failure with aging without confounding age-related tumors, hormonal changes and systemic illnesses. With aging, these animals have blunted circadian variations in luteinizing hormone (LH) and T, and decreased hypothalamic gonadotropin-releasing hormone (GnRH) synthetic capacity with preserved pituitary gonadotropin responses to GnRH. We found that aging male BN rats have increased peripheral and visceral adiposity associated with increased insulin and leptin levels, and decreased relative lean body mass and muscle mass. We found that these rats exhibit reduced food intake and body weight gain associated with decreased hypothalamic neuropeptide Y (NPY) gene expression in the arcuate nucleus (ARC), both during ad-libitum feeding and after a 72-h fast. Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted food intake and body weight gain response to fasting without affecting basal ARC NPY gene expression. These findings suggested that hyperinsulinemia and/or hyperleptinemia associated with aging may contribute to the age-related impairment in energy and weight regulation. Our studies suggest that the aging male BN rat is an excellent model to investigate the mechanisms underlying the age-associated changes in the neuroendocrine control of body composition, energy intake and body weight.

Anxiety, depression, hunger and body composition: III. Their relationships in obese patients.

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Menopause-associated differences in female fat patterning estimated by dual-energy X-ray absorptiometry

SummaryThe aim of the present study was to describe and quantify the typical changes in fat patterning from premenopause to postmenopause. The absolute and relative fat and lean body mass were estimated using dual-energy X-ray absorptiometry in 461 healthy non-obese females between the ages of 18 and 64 years (x = 43·2). Significant differences (p < 0·001) in absolute and relative fat mass, body weight and body mass index between pre-, peri- and postmenopausal females were observed. Postmenopausal women were significantly heavier (BMI, x = 26·8) than perimenopausal (BMI, x = 24·4) and younger and older premenopausal women (BMI, x = 22·8) and showed significantly higher fat percentages (fat% x = 38·1) in comparison to perimenopausal (x = 36·8) and premenopausal females (x = 31·4). Three indices, upper body composition index, lower body composition index and fat distribution index were calculated. Typical differences in fat distribution patterns between females of differential menopausal status were found. During the premenopausal phase a more gynoid type of fat distribution prevailed, during the postmenopausal phase a more android kind of fat distribution occurred predominantly. The fat distribution during the perimenopause can be interpreted as less gynoid than during the premenopause.

Body composition and energy intake: do overweight women overeat and underreport?

The relationship between energy consumption and body composition was evaluated in 63 women by use of energy-intake values that were precisely measured in a metabolic unit and corrected for deviations from energy balance. Energy requirement for the maintenance of body weight was not significantly correlated with adiposity expressed as percent body fat. However, energy requirement was positively associated with lean mass (p less than 0.0001) whereas fat mass added no predictive value to the same multivariate regression equation. Self-reported energy intake (before the experiments) was not correlated with lean mass and was underestimated by lean subjects at least as much as by obese subjects. Discrepant findings in the literature concerning relationships between obesity and energy intake may be explained by reporting error and by the relative lean mass of obese vs nonobese women but not by systematic underreporting unique to obese subjects.

Effects of dianabol and high-intensity sprint training on body composition of rats.

The effects on body composition and organ weights of anabolic steroid administration and of high-intensity sprint running, separately and in combination, were studied in young adult male rats. Dianabol (methandrostenolone) 1 mg/day for 8 weeks had no significant effects on muscle weight or lean body mass in either the trained or the sedentary animals. The program of sprint training resulted in a lower body weight, a lesser percentage of body fat (Runners, 8.5%, vs. sedentary, 13.5% P less than 0.01) and a greater relative lean body mass (runners, 91.5% vs. sedentry, 86.5%, P less than 0.01). We conclude from these results that (a) normal androgen levels in young, healthy male animals are sufficiently high so that the addition of a large dose of anabolic steroid does not result in stimulation of additional muscle growth, and (b) the changes in body composition induced by high-intensity, short-duration sprint training are qualitatively similar to those seen with endurance exercise training.