Growth hormone reduces inflammation in postmenopausal women with abdominal obesity: a 12-month, randomized, placebo-controlled trial.
ABSTRACT Abdominal obesity is associated with low GH secretion, elevated circulating markers of inflammation, and increased risk of cardiovascular disease.
The objective was to study the effect of GH treatment on inflammatory markers and vascular adhesion molecules in postmenopausal women with abdominal obesity.
Forty women aged 51-63 yr received GH (0.67 mg/d) in a randomized, double-blind, placebo-controlled, 12-month trial. Measurements of inflammatory markers [highly sensitive C-reactive protein (CRP), IL-6, and amyloid polypeptideA] and markers of endothelial dysfunction (soluble E-selectin, vascular adhesion molecule-1, intercellular molecule-1, and matrix metalloproteinase-9) were performed at baseline and after 6 and 12 months of treatment.
After 12 months, the mean IGF sd score was 0.9 +/- 1.5 and -0.8 +/- 0.6 in the GH and placebo groups, respectively. GH treatment reduced CRP and IL-6 levels compared with placebo (P = 0.03 and P = 0.05, respectively), whereas the markers of endothelial dysfunction were unaffected. Within the GH-treated group, a reduction was shown in CRP (4.3 +/- 4 to 3.0 +/- 3 mg/liter; P < 0.05) and in IL-6 (4.4 +/- 2 to 3.3 +/- 2 ng/liter; P < 0.01). In the GH-treated group, the decrease in CRP and IL-6 correlated with a reduction in visceral adipose tissue (r = 0.7, P < 0.001 and r = 0.5, P < 0.05, respectively).
GH treatment in postmenopausal women with abdominal obesity reduced serum markers of systemic inflammation. Circulating markers of endothelial dysfunction were unaffected by treatment.
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ABSTRACT: Context: Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are believed to be physiologic regulators of skeletal muscle mitochondria. Objective: The objective of this study was to examine the relationship between GH/IGF-I and skeletal muscle mitochondria in obese subjects with reduced GH secretion in more detail. Design: 15 abdominally obese men with reduced GH secretion were treated for 12 weeks with recombinant human GH (rhGH). Subjects underwent (31)Phosphorous-magnetic resonance spectroscopy to assess phosphocreatine (PCr) recovery as an in vivo measure of skeletal muscle mitochondrial function and percutaneous muscle biopsies to assess mRNA expression of IGF-I and mitochondrial related genes at baseline and 12 weeks. Results: At baseline, skeletal muscle IGF-I mRNA expression was significantly associated with PCr recovery (r=0.79; P=0.01) and nuclear respiratory factor-1 (NRF-1) (r=0.87; P=0.001), mitochondrial transcription factor A (TFAM) (r=0.86; P=0.001), peroxisome proliferator-activated receptor (PPAR)γ (r=0.72; P=0.02), and PPARα (r=0.75; P=0.01) mRNA expression, and trended to an association with peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) (r=0.59; P=0.07) mRNA expression. However, serum IGF-I concentration was not associated with PCr recovery or any mitochondrial gene expression (all P>0.10). Administration of rhGH increased both serum IGF-I (Change: 218±29μ g/l; P<0.0001) and IGF-I mRNA in muscle (Fold change: 2.1±0.3; P=0.002). Increases in serum IGF-I were associated with improvements in total body fat (r=-0.53; P=0.04), trunk fat (r=-0.55; P=0.03) and lean mass (r=0.58; P=0.02), but not with PCr recovery (P>0.10). Conversely, increase in muscle IGF-I mRNA was associated with improvements in PCr recovery (r=0.74; P=0.02), but not with body composition parameters (P>0.10). Conclusion: These data demonstrate a novel association of skeletal muscle mitochondria with muscle IGF-I mRNA expression, but independent of serum IGF-1 concentrations.The Journal of clinical endocrinology and metabolism. 11/2014;
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ABSTRACT: Emerging evidence demonstrates that high plasma C-reactive protein (CRP) levels or low plasma insulin-like growth factor 1 (IGF-1) concentrations may be separately associated with the increased risk of coronary artery disease or myocardial infarction. Interestingly, animal model studies and epidemiological investigations indicate that circulating IGF-1 and CRP levels have an inverse correlation. The present study aims to evaluate if IGF-1 can directly oppose the effects of CRP on endothelial cell (EC) activation. We found that IGF-1 rescues endothelial nitric oxide synthase activity and decreases the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. We also showed that IGF-1 antagonizes the effects of CRP by activating the PI3K/Akt pathway and suppressing the JNK/c-Jun and MAPK p38/ATF2 signaling pathways, rather than inhibiting ERK1/2 activity. These findings provide evidence of the physiopathological mechanisms of endothelial activation and novel insights into the protective properties of IGF-1.Molecular and Cellular Biochemistry 09/2013; · 2.33 Impact Factor
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ABSTRACT: Obesity is a major epidemic of our time and is associated with diseases such as metabolic syndrome, type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Although weight loss drugs, when accompanied by diet and exercise, could be a very helpful medical tool in treating obese or overweight patients, their usefulness has been questioned due to the complexity of this type of medication, which regards a plethora of issues such as efficacy and safety of the drug and also risks and benefits among different patients. In general, obesity drugs that target peripheral pathophysiological mechanisms can be divided into two main categories. The first category includes anti-obesity agents able to reduce or limit energy absorption, such as pancreatic lipase and microsomal triglyceride transfer protein inhibitors. The second category consists of a heterogeneous group of compounds aiming to decrease fat mass by increasing energy expenditure or by redistributing adipose tissue. Angiogenesis inhibitors, beta-3 receptor agonists, sirtuin-I activators, diazoxide and other molecules belong to this group. The glucagon-like peptide-1 receptor agonists consist the third category of peripheral anti-obesity agents discussed therein. This review aims to provide a general overview of the molecules and substances that are already or could potentially be used as peripheral anti-obesity drugs, the molecular mechanisms by which they act, as well as their current stage of development, production and/or availability.Obesity Reviews 02/2014; · 6.87 Impact Factor