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Effect of 14 days of experimental horizontal bed rest on circulating levels of irisin
Abstracts / Atherosclerosis 263 (2017) e111ee282
Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy Aim: The adipose organ is a complex and highly active metabolic and endocrine organ, and includes discrete anatomical depots of known differences in function and impact on obesity-associated metabolic complications. A sedentary lifestyle is associated to a quantitative and qualitative alteration of adipose tissue mass and function. Bed rest has been utilized as an experimental model to simulate physical inactivity and is known to produce alterations on visceral adipose tissue function, while gluteal adipose tissue has been studied to a lesser extent. The aim of our study was to investigate the impact of physical inactivity on gluteal adipose tissue gene expression in healthy subjects. Methods: A total of 7 subjects underwent gluteal adipose tissue biopsies before and after 14 days of bed rest; RNA was isolated and hybridized on RNA microarray chips; then in silico analysis was performed to find potential gene-disease associations. Results: A total of 308 genes were differently expressed after bed rest intervention; in silico analysis showed that 34 genes have been previously involved in cardiovascular and metabolic disorders. Among these, UCP3 and BMP7 have been shown to be involved in energy expenditure and adipose tissue 'browning'; TTR is a known transport. Moreover, several genes involved in inflammatory response such as CRP (C-Reactive Protein), IL1-beta and IL18 were differentially expressed after bedrest. Conclusions: In conclusion, our data suggest that gluteal adipose tissue may play an important role in the detrimental effect of physical inactivity and bed confinement on cardiovascular system and metabolism.
PO454. SELECTED ADIPOKINES IN PATIENTS WITH RELATIONSHIP TO SOLUBLE MARKERS DYSFUNCTION-A PILOT STUDY
TYPE 2 DIABETES: OF ENDOTHELIAL
David Karasek1, Jaromira Gajdova1, Veronika Kubickova2, Ondrej Krystynik1, Lubica Cibickova1, Helena Vaverkova1. 1 University Hospital, Third Department of Internal Medicine, Olomouc, Czech Republic; 2 University Hospital, Department of Clinical Biochemistry, Olomouc, Czech Republic Aim: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP9) and allograft inflammatory factor-1 (AIF-1) differently contribute to oxidative stress, chronic inflammation, insulin resistance and endothelial damage. The aim was to compare their levels in patients with type 2 diabetes and in healthy controls and to determine their relationship to soluble markers of endothelial dysfunction. Methods: 54 patients with type 2 diabetes (32 men, 22 women) and 21 healthy controls (8 men, 13 women) were included in the study. Adipokines, lipids, anthropological parameters, indicators of insulin resistance and also soluble markers of endothelial dysfunction - von Willebrand factor (vWF), plasminogen activator inhibitor -1 (PAI-1) and tissue plasminogen activator (t-PA) were measured. Results: Type 2 diabetics had significantly higher levels of A-FABP [50.0 (38.1-68.6) versus 28.6 (23.6-32.9) mg/l, p<0.001], vWF [133.1 (110.7163.2) versus 98.5 (84.4-125.0) %, p<0.01] and PAI [78.1 (41.2-106.5) versus 36.9 (27.5-41.9) ng/ml, p<0.001] and lower levels of adiponectin [5.9 (4.39.0) versus 11.3 (8.7-14.8) mg/l, p <0.001] compared to healthy controls. Differences in other adipokines were not statistically significant. Adiponectin correlated negatively with vWF levels (r¼-0.29, p<0.05) and PAI-1 (r¼-0.35, p<0.01), A-FABP positively with vWF (r¼0.45, p<0.01) PAI-1 (r¼0.46, p<0.01). FGF-21 correlated only with PAI-1 (r¼0.27, p<0.05). Conclusions: Patients with type 2 diabetes have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with markers of endothelial dysfunction and may contribute to the cardiovascular risk of these individuals.
PO455. EFFECT OF 14 DAYS OF EXPERIMENTAL HORIZONTAL BED REST ON CIRCULATING LEVELS OF IRISIN
e249
Daniela Francesconi1, Juana Maria Sanz1, Edoardo Dalla Nora1, Mario degli Luca Morieri2, Giovanni Zuliani1, Angelina Passaro1. 1 Universita studi di Ferrara, Department of Medical Science, Ferrara, Italy; 2 Joslin Diabetes Center, Research Division, Department of Genetic & Epidemiology, Boston, USA Aim: Irisin, a newly-discovered exercise-induced adipo-myokine, is supposed to play a role in “browning” of WAT leading to energy expenditure and metabolic improvement. Acute inactivity perturbs muscle function and is linked to many negative outcomes. To date many research investigated role of exercise on serum irisin levels, but no data exist concerning acute immobilization Methods: We evaluated circulating Irisin at basal, after 14 days of bed rest (BR14) and 14 days of recovery (R14) in 7 “Younger” (23±3 yo) and 16 “Older” (59±3 yo) healthy subjects. All subjects underwent anthropometric, body composition and blood samples analysis. Results: Basal irisin was similar in the two groups (Y4.58 vs O5.01 ng/ml; p¼0.74) and correlated with BMI (R 0.43, p¼0.04), muscle mass (R0.47, p¼0.02) and FFM (R 0.39, p¼0.01). A negative correlation with cholesterol (R-0.44, p¼0.04) and c-LDL (R-0.46, p¼0.03) was observed. At BR14, irisin increased in Older (Basal 5.01, BR14 7.06 mg/l; p¼0.013) returning to basal levels at R14. The increase, in younger, was not significant (Basal 4.58, BR14 6.07 mg/l, p¼0.16). After bed rest, a decrease of BMI, FFM, muscle mass and an increase of FM was observed in both groups. No significant correlation between body composition or lipid profile changes and the variation of irisin was found. Conclusions: At steady state serum irisin is related to muscle mass. Acute immobilization represents a threat for muscle, during which the increase in irisin levels are independent of muscle mass reduction. We speculate that this could represent a response of muscle tissue to preserve its function.
PO456. GENE EXPRESSION REGIONAL SUBCUTANEOUS ADIPOSE TISSUE
DIFFERENCES
IN
HUMAN
Edoardo Dalla Nora, Maria-Agata Miselli, Juana Maria Sanz, Mario Luca Morieri, Rossella Colonna, Giovanni Zuliani, Angelina Passaro. Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy Aim: Previous studies demonstrated that adipocytes from visceral and subcutaneous depots have distinct metabolic and functional characteristics. These regional differences have a key role in the pathogenesis of obesity-related diseases. However, the possible heterogeneity between different subcutaneous regions has not been extensively investigated. Here we studied global mRNA expression in g-SAT and a-SAT with a microarray approach in order to detect regional differences in gene expression. Methods: RNA was isolated from g-SAT and a-SAT biopsy from eight healthy subjects, and hybridized on RNA microarray chips; in silico analysis with bioinformatics database support was then performed. Results: A total of 131 genes were significantly and differently (>1.5 fold change, p<0.05) expressed in a-SAT and g-SAT. Expression profiling and in silico analysis revealed differences in expression of 18 coding genes previously connected to type 2 diabetes, and several HOX genes, and among these, two molecular signature of visceral adipocyte lineage (HOXA5 and NR2F1) were up-regulated in a-SAT versus g-SAT. Conclusions: Our study shows that g-SAT and a-SAT have distinct expression profiles. The finding of a different expression of HOX genes, fundamental during the embryo development, suggests an early regional differentiation, and the higher expression of HOXA5 and NR2F1 in a-SAT suggests that this subcutaneous adipose depot could be more similar to VAT than g-SAT. Furthermore, the finding that a consistent number of genes previously correlated to type 2 diabetes enforces our hypotesis that we should look at SAT as composed of distinct depots with possibly different impact in obesity associated metabolic complications.
Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy Aim: The adipose organ is a complex and highly active metabolic and endocrine organ, and includes discrete anatomical depots of known differences in function and impact on obesity-associated metabolic complications. A sedentary lifestyle is associated to a quantitative and qualitative alteration of adipose tissue mass and function. Bed rest has been utilized as an experimental model to simulate physical inactivity and is known to produce alterations on visceral adipose tissue function, while gluteal adipose tissue has been studied to a lesser extent. The aim of our study was to investigate the impact of physical inactivity on gluteal adipose tissue gene expression in healthy subjects. Methods: A total of 7 subjects underwent gluteal adipose tissue biopsies before and after 14 days of bed rest; RNA was isolated and hybridized on RNA microarray chips; then in silico analysis was performed to find potential gene-disease associations. Results: A total of 308 genes were differently expressed after bed rest intervention; in silico analysis showed that 34 genes have been previously involved in cardiovascular and metabolic disorders. Among these, UCP3 and BMP7 have been shown to be involved in energy expenditure and adipose tissue 'browning'; TTR is a known transport. Moreover, several genes involved in inflammatory response such as CRP (C-Reactive Protein), IL1-beta and IL18 were differentially expressed after bedrest. Conclusions: In conclusion, our data suggest that gluteal adipose tissue may play an important role in the detrimental effect of physical inactivity and bed confinement on cardiovascular system and metabolism.
PO454. SELECTED ADIPOKINES IN PATIENTS WITH RELATIONSHIP TO SOLUBLE MARKERS DYSFUNCTION-A PILOT STUDY
TYPE 2 DIABETES: OF ENDOTHELIAL
David Karasek1, Jaromira Gajdova1, Veronika Kubickova2, Ondrej Krystynik1, Lubica Cibickova1, Helena Vaverkova1. 1 University Hospital, Third Department of Internal Medicine, Olomouc, Czech Republic; 2 University Hospital, Department of Clinical Biochemistry, Olomouc, Czech Republic Aim: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP9) and allograft inflammatory factor-1 (AIF-1) differently contribute to oxidative stress, chronic inflammation, insulin resistance and endothelial damage. The aim was to compare their levels in patients with type 2 diabetes and in healthy controls and to determine their relationship to soluble markers of endothelial dysfunction. Methods: 54 patients with type 2 diabetes (32 men, 22 women) and 21 healthy controls (8 men, 13 women) were included in the study. Adipokines, lipids, anthropological parameters, indicators of insulin resistance and also soluble markers of endothelial dysfunction - von Willebrand factor (vWF), plasminogen activator inhibitor -1 (PAI-1) and tissue plasminogen activator (t-PA) were measured. Results: Type 2 diabetics had significantly higher levels of A-FABP [50.0 (38.1-68.6) versus 28.6 (23.6-32.9) mg/l, p<0.001], vWF [133.1 (110.7163.2) versus 98.5 (84.4-125.0) %, p<0.01] and PAI [78.1 (41.2-106.5) versus 36.9 (27.5-41.9) ng/ml, p<0.001] and lower levels of adiponectin [5.9 (4.39.0) versus 11.3 (8.7-14.8) mg/l, p <0.001] compared to healthy controls. Differences in other adipokines were not statistically significant. Adiponectin correlated negatively with vWF levels (r¼-0.29, p<0.05) and PAI-1 (r¼-0.35, p<0.01), A-FABP positively with vWF (r¼0.45, p<0.01) PAI-1 (r¼0.46, p<0.01). FGF-21 correlated only with PAI-1 (r¼0.27, p<0.05). Conclusions: Patients with type 2 diabetes have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with markers of endothelial dysfunction and may contribute to the cardiovascular risk of these individuals.
PO455. EFFECT OF 14 DAYS OF EXPERIMENTAL HORIZONTAL BED REST ON CIRCULATING LEVELS OF IRISIN
e249
Daniela Francesconi1, Juana Maria Sanz1, Edoardo Dalla Nora1, Mario degli Luca Morieri2, Giovanni Zuliani1, Angelina Passaro1. 1 Universita studi di Ferrara, Department of Medical Science, Ferrara, Italy; 2 Joslin Diabetes Center, Research Division, Department of Genetic & Epidemiology, Boston, USA Aim: Irisin, a newly-discovered exercise-induced adipo-myokine, is supposed to play a role in “browning” of WAT leading to energy expenditure and metabolic improvement. Acute inactivity perturbs muscle function and is linked to many negative outcomes. To date many research investigated role of exercise on serum irisin levels, but no data exist concerning acute immobilization Methods: We evaluated circulating Irisin at basal, after 14 days of bed rest (BR14) and 14 days of recovery (R14) in 7 “Younger” (23±3 yo) and 16 “Older” (59±3 yo) healthy subjects. All subjects underwent anthropometric, body composition and blood samples analysis. Results: Basal irisin was similar in the two groups (Y4.58 vs O5.01 ng/ml; p¼0.74) and correlated with BMI (R 0.43, p¼0.04), muscle mass (R0.47, p¼0.02) and FFM (R 0.39, p¼0.01). A negative correlation with cholesterol (R-0.44, p¼0.04) and c-LDL (R-0.46, p¼0.03) was observed. At BR14, irisin increased in Older (Basal 5.01, BR14 7.06 mg/l; p¼0.013) returning to basal levels at R14. The increase, in younger, was not significant (Basal 4.58, BR14 6.07 mg/l, p¼0.16). After bed rest, a decrease of BMI, FFM, muscle mass and an increase of FM was observed in both groups. No significant correlation between body composition or lipid profile changes and the variation of irisin was found. Conclusions: At steady state serum irisin is related to muscle mass. Acute immobilization represents a threat for muscle, during which the increase in irisin levels are independent of muscle mass reduction. We speculate that this could represent a response of muscle tissue to preserve its function.
PO456. GENE EXPRESSION REGIONAL SUBCUTANEOUS ADIPOSE TISSUE
DIFFERENCES
IN
HUMAN
Edoardo Dalla Nora, Maria-Agata Miselli, Juana Maria Sanz, Mario Luca Morieri, Rossella Colonna, Giovanni Zuliani, Angelina Passaro. Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy Aim: Previous studies demonstrated that adipocytes from visceral and subcutaneous depots have distinct metabolic and functional characteristics. These regional differences have a key role in the pathogenesis of obesity-related diseases. However, the possible heterogeneity between different subcutaneous regions has not been extensively investigated. Here we studied global mRNA expression in g-SAT and a-SAT with a microarray approach in order to detect regional differences in gene expression. Methods: RNA was isolated from g-SAT and a-SAT biopsy from eight healthy subjects, and hybridized on RNA microarray chips; in silico analysis with bioinformatics database support was then performed. Results: A total of 131 genes were significantly and differently (>1.5 fold change, p<0.05) expressed in a-SAT and g-SAT. Expression profiling and in silico analysis revealed differences in expression of 18 coding genes previously connected to type 2 diabetes, and several HOX genes, and among these, two molecular signature of visceral adipocyte lineage (HOXA5 and NR2F1) were up-regulated in a-SAT versus g-SAT. Conclusions: Our study shows that g-SAT and a-SAT have distinct expression profiles. The finding of a different expression of HOX genes, fundamental during the embryo development, suggests an early regional differentiation, and the higher expression of HOXA5 and NR2F1 in a-SAT suggests that this subcutaneous adipose depot could be more similar to VAT than g-SAT. Furthermore, the finding that a consistent number of genes previously correlated to type 2 diabetes enforces our hypotesis that we should look at SAT as composed of distinct depots with possibly different impact in obesity associated metabolic complications.