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Pharmacology of manipulating lean body mass.

ABSTRACT: Dysfunction and wasting of skeletal muscle as a consequence of illness decreases the length and quality of life. Currently, there are few, if any, effective treatments available to address these conditions. Hence, the existence of this unmet medical need has fuelled large scientific efforts. Fortunately, these efforts have shown many of the underlying mechanisms adversely affecting skeletal muscle health. With increased understanding have come breakthrough disease-specific and broad spectrum interventions, some progressing through clinical development. The present review focuses its attention on the role of the antagonistic process regulating skeletal muscle mass before branching into prospective promising therapeutic targets and interventions. Special attention is given to therapies in development against cancer cachexia and Duchenne muscular dystrophy before closing remarks on design and conceptualization of future therapies are presented to the reader.

SUBMITTER: Sepulveda PV

PROVIDER: S-EPMC4383600 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Pharmacology of manipulating lean body mass.

Sepulveda Patricio V PV Bush Ernest D ED Baar Keith K

Clinical and experimental pharmacology & physiology 20150101 1

Dysfunction and wasting of skeletal muscle as a consequence of illness decreases the length and quality of life. Currently, there are few, if any, effective treatments available to address these conditions. Hence, the existence of this unmet medical need has fuelled large scientific efforts. Fortunately, these efforts have shown many of the underlying mechanisms adversely affecting skeletal muscle health. With increased understanding have come breakthrough disease-specific and broad spectrum int ...[more]

PMID: 25311629

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Project description:BackgroundLittle is known about the association of changes in two body components, muscle and fat mass, with the risk of cardiovascular disease (CVD) among young adults. We investigated the association of changes in predicted lean body mass index (LBMI), appendicular skeletal muscle mass index (ASMI), and body fat mass index (BFMI) with the development of CVD among young adults.MethodsThis nationwide, population-based cohort study included 3 727 738 young adults [2 406 046 (64.5%) men and 1 321 692 (35.5%) women] aged 20-39 years without a previous history of CVD who underwent two health screening examinations during 2009-2010 and 2011-2012. Using validated and robust prediction equations, we calculated the changes in predicted LBMI, ASMI, and BFMI from the first to the second examinations.ResultsThe mean (SD) age was 32.2 (4.9) years, and 2 406 046 (64.5%) of the participants were men. A total of 23 344 CVD events were detected during 22 257 632 person-years of follow-up. Each 1 kg/m2 increase in predicted LBMI and ASMI change was associated with a reduced risk of CVD among men [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI) 0.82-0.91; aHR: 0.76, 95% CI 0.69-0.82, respectively] and women (aHR: 0.77, 95% CI 0.63-0.95; aHR: 0.75, 95% CI 0.59-0.96). Each 1 kg/m2 increase in predicted BFMI change was associated with an increased risk of CVD among men (aHR: 1.16, 95% CI 1.10-1.22) and women (aHR: 1.32, 95% CI 1.06-1.65). In both sexes, decreases in predicted LBMI and ASMI were associated with greater CVD risk, and decreased predicted BFMI was associated with a reduced CVD risk. Those who maintained their BMI between -1 and +1 kg/m2 also had a decreased risk of CVD per 1 kg/m2 increase in predicted LBMI and ASMI change among men (aHR: 0.86, 95% CI 0.80-0.92; aHR: 0.85, 95% CI 0.76-0.95) and women (aHR: 0.62, 95% CI 0.47-0.83; aHR: 0.59, 95% CI 0.44-0.80) and had a greater risk of CVD per 1 kg/m2 increase in predicted BFMI change among men (aHR: 1.17, 95% CI 1.10-1.25) and women (aHR: 1.64, 95% CI 1.20-2.23). Regardless of changes in weight, such as from normal to obese or vice versa, these results were consistent.ConclusionsAmong young adults, increased predicted muscle mass or decreased predicted fat mass were associated with a reduced risk of development of CVD. Decreased predicted muscle mass or increased predicted fat mass were associated with an elevated risk of development of CVD.

Project description:Obesity and physical inactivity are major public health problems. We studied the associations between measures of adiposity, lean body mass, leisure time physical activity (LTPA), and death in those with and without chronic kidney disease (CKD).Associations between body mass index (BMI), waist circumference (WC), percent body fat, lean body mass (assessed with Dual-Energy X-ray Absorptiometry[DEXA]), leisure time physical activity (LTPA) and death were examined using the National Health and Nutrition Examination Surveys (NHANES 1999-2004). All-cause mortality was ascertained by linkage of NHANES files with the National Death Index.9,433 non-CKD participants and 2,153 CKD participants who had fat mass measured using DEXA, BMI, WC, LTPA and mortality data were included. After adjusting for demographics, comorbid conditions, kidney function measures, C-Reactive Protein (CRP), and sodium intake there was no significant risk for death noted with higher WC, fat mass and BMI in those with and without CKD. When examining normal, overweight, and obese groups based on BMI criteria, being overweight (BMI 25-29.9 kg/m2) was associated with lower risk of death in those without CKD (Hazard ratio 0.62, 95% CI 0.40, 0.95). Higher lean body mass was associated with lower risk for death in those without kidney disease but not in the CKD population. There was a significantly higher risk for death among those who did not meet the minimum LTPA goals compared to those who met or exceeded the recommended activity levels (>450 MET/min/week) in those with and without CKD (CKD Hazard ratio: 1.36, 95% CI 1.003, 1.85; non-CKD HR 1.65, 95% CI 1.21, 2.26).In a representative sample of the US population, higher LTPA levels and lean body mass were associated with lower mortality in those without kidney disease. In CKD, higher LTPA was associated with lower risk of death. There was no association between adiposity measures and death in those with and without CKD except for lower mortality associated with overweight among those without CKD. The data suggests the need to develop programs to facilitate an increase in physical activity in people with and without kidney disease.

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Pharmacology of manipulating lean body mass.

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Pharmacology of manipulating lean body mass.

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