TY - JOUR
T1 - Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?
AU - Mingrone, G.
AU - Manco, M.
AU - Calvani, M.
AU - Castagneto, M.
AU - Naon, D.
AU - Zorzano, A.
PY - 2005/10
Y1 - 2005/10
N2 - Aims/hypothesis: In obesity the cellular capacity to switch from using lipid to carbohydrate and vice versa as the energy substrate, known as 'metabolic flexibility', is impaired. Mitofusin 2 (MFN2), a mitochondrial membrane protein, seems to contribute to the maintenance and operation of the mitochondrial network, and its expression is reduced in obesity. The aim of this study was to verify whether MFN2 might be implicated in the metabolic inflexibility of obesity. Materials andmethods: Insulin sensitivity was measured in six morbidly obese women before and 2 years after malabsorptive bariatric surgery (BMI 53.3±10.5 vs 30.3±4.0 kg/m2). Skeletal muscle MFN2, SLC2A4 (formerly known as GLUT4), COX3 (encoding cytochrome c oxidase subunit III) and CS (encoding citrate synthase) mRNA levels were measured by real-time PCR. Results: Following bilio-pancreatic surgery, significant increases in MFN2 mRNA (from 0.4±0.2 to 1.7±1.1 arbitrary units [AU], p=0.019) and SLC2A4 mRNA (0.38±0.12 to 0.76±0.24 AU, p=0.04) were observed, while increases in COX3 mRNA (from 14.2±6.4 to 20.2±12.5 AU) and CS mRNA (from 0.4±0.1 to 0.7±0.3 AU) failed to reach statistical significance. Insulin-mediated whole-body glucose uptake significantly (p-1 min-1 and glucose oxidation rose from 11.1±2.1 to 37.7±4.7 μmol kg fat-free mass-1 min-1 (p2=0.92, p2=0.80, p2=0.61, p
AB - Aims/hypothesis: In obesity the cellular capacity to switch from using lipid to carbohydrate and vice versa as the energy substrate, known as 'metabolic flexibility', is impaired. Mitofusin 2 (MFN2), a mitochondrial membrane protein, seems to contribute to the maintenance and operation of the mitochondrial network, and its expression is reduced in obesity. The aim of this study was to verify whether MFN2 might be implicated in the metabolic inflexibility of obesity. Materials andmethods: Insulin sensitivity was measured in six morbidly obese women before and 2 years after malabsorptive bariatric surgery (BMI 53.3±10.5 vs 30.3±4.0 kg/m2). Skeletal muscle MFN2, SLC2A4 (formerly known as GLUT4), COX3 (encoding cytochrome c oxidase subunit III) and CS (encoding citrate synthase) mRNA levels were measured by real-time PCR. Results: Following bilio-pancreatic surgery, significant increases in MFN2 mRNA (from 0.4±0.2 to 1.7±1.1 arbitrary units [AU], p=0.019) and SLC2A4 mRNA (0.38±0.12 to 0.76±0.24 AU, p=0.04) were observed, while increases in COX3 mRNA (from 14.2±6.4 to 20.2±12.5 AU) and CS mRNA (from 0.4±0.1 to 0.7±0.3 AU) failed to reach statistical significance. Insulin-mediated whole-body glucose uptake significantly (p-1 min-1 and glucose oxidation rose from 11.1±2.1 to 37.7±4.7 μmol kg fat-free mass-1 min-1 (p2=0.92, p2=0.80, p2=0.61, p
KW - Glucose oxidation
KW - Insulin sensitivity
KW - Metabolic inflexibility
KW - Mitofusin-2 mRNA expression
KW - Morbid obesity
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U2 - 10.1007/s00125-005-1918-9
DO - 10.1007/s00125-005-1918-9
M3 - Article
C2 - 16160866
AN - SCOPUS:26244456362
VL - 48
SP - 2108
EP - 2114
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 10
ER -