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Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene ( PGC1A ) during weight loss is related to insulin sensitivity but not to energy expenditure

Gastaldi, G. ; Russell, A. ; Golay, A. ; Giacobino, J.-P ; Habicht, F. ; Barthassat, V. ; Muzzin, P. ; Bobbioni-Harsch, E.

In: Diabetologia, 2007, vol. 50, no. 11, p. 2348-2355

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    Titre
    • Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene ( PGC1A ) during weight loss is related to insulin sensitivity but not to energy expenditure
    Auteur
    • Gastaldi, G.. Service of Therapeutic Education for Chronic Diseases, Geneva University Hospital, 24, Rue Micheli du Crest, 1211, Geneva, Switzerland
    • Russell, A.. Center for Physical Activity and Nutrition (C-PAN), School of Exercise and Nutrition Sciences, Deakin University, Melbourne, VIC, Australia
    • Golay, A.. Service of Therapeutic Education for Chronic Diseases, Geneva University Hospital, 24, Rue Micheli du Crest, 1211, Geneva, Switzerland
    • Giacobino, J.-P. Department of Cell Physiology and Metabolism, Geneva Medical School, Geneva, Switzerland
    • Habicht, F.. Service of Therapeutic Education for Chronic Diseases, Geneva University Hospital, 24, Rue Micheli du Crest, 1211, Geneva, Switzerland
    • Barthassat, V.. Service of Therapeutic Education for Chronic Diseases, Geneva University Hospital, 24, Rue Micheli du Crest, 1211, Geneva, Switzerland
    • Muzzin, P.. Department of Cell Physiology and Metabolism, Geneva Medical School, Geneva, Switzerland
    • Bobbioni-Harsch, E.. Service of Therapeutic Education for Chronic Diseases, Geneva University Hospital, 24, Rue Micheli du Crest, 1211, Geneva, Switzerland
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:312132
    Summary
    Aims/hypothesis: We investigated whether skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1A; also known as PPARGC1A) and its target mitofusin-2 (MFN2), as well as carnitine palmitoyltransferase-1 (CPT1; also known as carnitine palmitoyltransferase 1A [liver] [CPT1A]) and uncoupling protein (UCP)3, are involved in the improvement of insulin resistance and/or in the modification of energy expenditure during surgically induced massive weight loss. Materials and methods: Seventeen morbidly obese women (mean BMI: 45.9 ± 4kg/m2) were investigated before, and 3 and 12months after, Roux-en-Y gastric bypass (RYGB). We evaluated insulin sensitivity by the euglycaemic-hyperinsulinaemic clamp, energy expenditure and substrate oxidation by indirect calorimetry, and muscle mRNA expression by PCR. Results: Post-operatively, PGC1A was enhanced at 3 (p = 0.02) and 12months (p = 0.03) as was MFN2 (p = 0.008 and p = 0.03 at 3 and 12months respectively), whereas UCP3 was reduced (p = 0.03) at 12months. CPT1 did not change. The expression of PGC1A and MFN2 were strongly (p < 0.0001) related. Insulin sensitivity, which increased after surgery (p = 0.002 at 3, p = 0.003 at 12months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3months post-operatively (p = 0.001 vs before RYGB), remaining unchanged thereafter until 12months. CPT1 and UCP3 were not significantly related to the modifications of energy expenditure or of lipid oxidation rate. Conclusions/interpretation: Weight loss upregulates PGC1A, which in turn stimulates MFN2 expression. MFN2 expression significantly and independently contributes to the improvement of insulin sensitivity. UCP3 and CPT1 do not seem to influence energy expenditure after RYGB