leptin and Sarcopenia

Lung transplantation offers patients with end-stage lung disease an opportunity for a better quality of life, but with limited organ availability it is paramount that selected patients have the best opportunity for successful outcomes. Nutrition plays a central role in post-surgical outcomes and, historically, body mass index (BMI) has been used as the de facto method of assessing a lung transplant candidate's nutritional status. Here, we review the historical origins of BMI in lung transplantation, summarize the current BMI literature, and review studies of alternative/complementary body composition assessment tools, including lean psoas area, creatinine-height index, leptin, and dual x-ray absorptiometry. These body composition measures quantify lean body mass versus fat mass and may provide a more comprehensive analysis of a patient's nutritional state than BMI alone.

Topics: Absorptiometry, Photon; Body Composition; Body Mass Index; Leptin; Lung Transplantation; Muscle, Skeletal; Nutrition Assessment; Nutritional Status; Patient Selection; Preoperative Period; Sarcopenia; Transplant Recipients; Treatment Outcome

Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc.

Topics: Animals; Anorexia Nervosa; Appetite; Cachexia; Deficiency Diseases; Energy Intake; Ghrelin; Humans; Hypothalamus; Leptin; Patents as Topic; Sarcopenia; Trace Elements; Zinc

Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population.

Topics: Aged; Appetite; Basal Metabolism; Beverages; Blood Glucose; Breakfast; Caseins; Cross-Over Studies; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Ghrelin; Humans; Insulin; Leptin; Male; Sarcopenia; Single-Blind Method; Sleep; Time Factors

Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator -1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.

Topics: Adipokines; Adiponectin; Humans; Leptin; Muscles; Sarcopenia

Sarcopenic elderly present low muscle mass and strength, however, it is not clear if the inflammatory and metabolic profile is more related to low lean mass or high fat mass in sarcopenic and non-sarcopenic overfat elderly.. To verify the difference in inflammatory and metabolic responses in sarcopenic and non-sarcopenic overfat elderly and the relationship between these markers, body composition, and strength in this population.. Fifty-seven elderly were divided into two groups: sarcopenic (n = 30) and non-sarcopenic (n = 27). Body composition was evaluated with octopolar bioimpedance. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, glucose, cortisol, leptin, adiponectin, Plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-6, IL-8, and IL-10 were assessed. The handgrip test was used to evaluate strength.. When comparing the inflammatory profile, sarcopenic individuals showed greater adiponectin concentration (p = 0.019), adiponectin/fat mass ratio (p < 0.001), adiponectin/visceral fat (p < 0.001), and higher PAI-1 (p = 0.019) than non-sarcopenic overfat elderly. After adjusting the inflammatory profile by skeletal muscle mass the significant differences between groups were maintained (p < 0.05) but no significant differences between groups were observed when adjusting by fat mass, despite a tendency to a significant difference for adiponectin concentration (p = 0.06). In addition, after adjusting leptin by fat mass there was a statistically significant lower concentration in the sarcopenic compared to non-sarcopenic overfat elderly.. Non-sarcopenic overfat elderly presented lower anti-inflammatory and anti-atherogenic responses than sarcopenic elderly. Furthermore, fat mass but not skeletal muscle mass seem to change these responses.

Topics: Adiponectin; Adipose Tissue; Aged; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Leptin; Male; Muscle Strength; Muscle, Skeletal; Obesity; Plasminogen Activator Inhibitor 1; Sarcopenia

Chronic inflammation with aging contributes to sarcopenia. Previous studies have suggested that the accumulation of adipose tissue in skeletal muscle, referred to as intermuscular adipose tissue (IMAT), increases with age and is associated with inflammation. However, the mechanism governing ectopic inflammation in skeletal muscle due to aging is not fully understood. Leptin, an adipocytokine derived from adipose tissue, is an important mediator of inflammatory processes. We examined changes in leptin levels with age and whether leptin contributes to ectopic inflammation.. To evaluate ectopic inflammation in skeletal muscle, we measured alterations to the expression of inflammatory cytokine genes (Il1b, Il6, and Tnfa) and muscle break down-related gene (MuRF1 and Atrogin1) in the quadricep muscles of young (10 weeks) and aged (48 weeks) female rats using quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR). Histological examination was performed to identify the extent of IMAT. Leptin mRNA and leptin protein expression were examined using Q-RT-PCR and enzyme-linked immunosorbent assay, respectively. The effect of leptin on the mRNA expression of Il1b, Il6, and Tnfa in quadricep muscle-derived cells was also examined by stimulating the cells with 0 (control), 1, or 10 μg/mL rat recombinant leptin using Q-RT-PCR.. Aged rats had significantly higher Il6, MuRF1, and Atrogin1 but not Il1b and Tnfa, expression and greater levels of IMAT in their quadricep muscles than young rats. Aged rats also had significantly higher leptin expression and leptin protein concentration in their quadricep muscles than young rats. The addition of exogenous leptin to quadricep muscle-derived cells significantly increased the gene expression of Il1b and Il6 but not Tnfa.. Our results suggest that elevated leptin levels due to aging cause ectopic inflammation through IL-6 in the skeletal muscle of aged rats.

Topics: Adipose Tissue; Aging; Animals; Disease Models, Animal; Female; Interleukin-6; Leptin; Models, Animal; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Sarcopenia

The associations between serum leptin, vitamin D status, sarcopenic obesity, muscle strength and physical performance in osteoarthritis (OA) remain uncertain.. To analyse the relationships between serum leptin, vitamin D status, muscle strength and physical performance in OA patients.. A total of 208 knee OA patients were enrolled. Serum leptin, vitamin D, muscle strength and physical performance were evaluated.. OA patients with sarcopenic obesity had significantly higher serum leptin levels than those with non-sarcopenic obesity. In addition, knee OA patients with sarcopenic obesity displayed low grip strength and poor physical performance. Furthermore, high serum leptin was negatively associated with vitamin D and physical performance.. Serum leptin levels were correlated with low vitamin D, reduced muscle strength and functional impairment, suggesting that serum leptin might serve as a biomarker reflecting physical performance in OA patients.

Topics: Aged; Biomarkers; Female; Humans; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Muscle Strength; Obesity; Osteoarthritis, Knee; Physical Fitness; Sarcopenia; Vitamin D

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels.. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined.. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease.. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels.

Topics: Adiponectin; Aged; Albuminuria; Ankle Brachial Index; Blood Flow Velocity; Body Composition; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Risk Factors; Sarcopenia; Vascular Stiffness

Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)-based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation.. We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates.. Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9), and class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI < 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10-66%). Class II-III obesity (BMI ≥ 35 kg/m(2)) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m(2) was 26% sensitive and 97% specific for total body fat-defined obesity.. A BMI of 30.0-34.9 kg/m(2) is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m(2) may no longer contraindicate lung transplantation.

Topics: Body Composition; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Female; Humans; Leptin; Lung Diseases; Lung Transplantation; Male; Middle Aged; Obesity; Retrospective Studies; Sarcopenia; Survival Rate; United States

The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA) and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women), participating in a medical check-up program. Visceral obesity was defined as visceral fat area >100 cm², and sarcopenia was defined as < (one standard deviation--mean of thigh muscle CSA/body weight of young subjects [aged <50 years]).Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (β = -0.28, p<0.0001) and women (β = -0.20, p<0.0001), even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia.

Topics: Adipocytes; Aged; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Muscle Cells; Muscle, Skeletal; Obesity, Abdominal; Sarcopenia

Postmenopausal women develop often obesity which may be prevented by 20-OH-Ecdysone (Ecd). This was investigated in ovariectomized (ovx) rats. They were orally treated with 3 doses of Ecd (18, 56 or 116 mg/day/animal). Positive controls received 159 microg estradiol (E2). Quantitative computer tomography at the level of the abdomen and the metaphysis of the tibia allowed estimation of surface, fat depots and muscles. The highest dose of Ecd resulted in serum concentrations of 0.4 x 10(-6)M. Serum E2 concentrations in the positive controls were 73.3+/-24.41 pg/ml. E2 but not Ecd stimulated uterine weights. Under Ecd ovx animals gained less fat but had more muscle mass. Serum TSH, T4 and T3 levels remained unaffected while E2 treatment increases T4 but decreases T3 levels. Ecd at the lowest dose lowered serum LDL and did not result in increased serum triglycerides, an effect seen in the E2 treated rats. At the Ecd highest dose serum HDL was higher than in the controls. In conclusion Ecd has beneficial effects on fat and muscle tissue and may be able to prevent the metabolic syndrome and sarcopenia by a non-estrogenic mechanism.

Topics: Animals; Body Composition; Dose-Response Relationship, Drug; Ecdysterone; Estrogens; Female; Hindlimb; Intra-Abdominal Fat; Leptin; Lipids; Metabolic Syndrome; Obesity; Organ Size; Ovariectomy; Postmenopause; Rats; Rats, Sprague-Dawley; Sarcopenia; Thyroid Hormones; Thyrotropin; Uterus