Intramyocellular lipids; Insulin resistance; Aging; Exercise; Intrahepatocellular lipids; Obesity; Mitochondria
Dubé John J., Broskey Nicholas T., Despines Alex A., Stefanovic-Racic Maya, Toledo Frederico G.S., Goodpaster Bret H., Amati Francesca (2016), Muscle characteristics and substrate energetics in lifelong endurance athletes, in Medicine & Science in Sports & Exercise
, 48(3), 472-80.
Broskey N. T., Boss A., Fares E. J., Greggio C., Gremion G., Schluter L., Hans D., Kreis R., Boesch C., Amati F. (2015), Exercise efficiency relates with mitochondrial content and function in older adults, in Physiol Rep
, 3, e12418.
Diserens G., Vermathen M., Precht C., Broskey N. T., Boesch C., Amati F., Dufour J. -F., Vermathen P. (2015), Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study, in ANALYST
, 140(1), 272-279.
Broskey Nicholas T., Boss Andreas, Kreis Roland, Boesch Chris, Amati Francesca (2014), Do Skeletal Muscle Mitochondria Play A Role In Making Us More Efficient For Endurance Exercise?, in MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
, 46(5), 753-753.
Amati Francesca, Broskey Nicholas T., Carnero Elvis A. (2014), Evidence of systematic and proportional error in a widely used glucose oxidase analyser: impact for clinical research?, in CLINICAL ENDOCRINOLOGY
, 80(5), 768-770.
Amati F., Greggio C., Broskey N. T., Janssens W., Boss A., Kreis R., Boesch C. (2014), Improvement in insulin sensitivity following exercise training is independent of mitochondrial changes in older adults, in DIABETOLOGIA
, 57, 254-254.
Broskey Nicholas T., Greggio Chiara, Boss Andreas, Boutant Marie, Dwyer Andrew, Schlueter Leopold, Hans Didier, Gremion Gerald, Kreis Roland, Boesch Chris, Canto Carles, Amati Francesca (2014), Skeletal Muscle Mitochondria in the Elderly: Effects of Physical Fitness and Exercise Training (vol 99, pg 1852, 2014), in JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
, 99(7), 2619-2619.
Broskey N. T., Fares E-J., Greggio C., Amati F. (2014), The effect of chronic exercise training on exercise efficiency and fat oxidation in older previously sedentary adults, in DIABETOLOGIA
, 57, 254-255.
Amati Francesca, Widmann Christian (2014), Triglyceride and HDL: the entangled pair, in CURRENT OPINION IN LIPIDOLOGY
, 25(5), 404-405.
Greggio C., Broskey N. T., Boutant M., Canto C., Amati F. (2013), Effect of chronic exercise on skeletal muscle mitochondria dynamics in older adults, in DIABETOLOGIA
, 56, 32-32.
Broskey Nicholas T., Boss Andreas, Fares Elie-Jacques, Kreis Roland, Gremion Gerald, Boesch Chris, Amati Francesca (2013), Exercise Capacity In Older Adults: A Matter Of Mitochondrial Function, Content Or Efficiency?, in MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
, 45(5), 517-518.
Broskey Nicholas T., Daraspe Jean, Humbel Bruno M., Amati Francesca (2013), Skeletal muscle mitochondrial and lipid droplet content assessed with standardized grid sizes for stereology, in JOURNAL OF APPLIED PHYSIOLOGY
, 115(5), 765-770.
Broskey N. T., Fares E. -J., Greggio C., Amati F. (2013), The effect of exercise training on skeletal muscle mitochondrial content in older adults correlates with exercise efficiency and fat oxidation, in DIABETOLOGIA
, 56, 32-32.
Insulin resistance is a crucial factor for the development of type 2 diabetes and a major health problem for older adults. Obesity has been linked with insulin resistance. The increasing prevalence of obesity and type 2 diabetes in the older population has important consequences on the morbidity and mortality as well as on the economic burden on our societies. Ectopic lipid depositions, defined as an excess accumulation of triglycerides in non adipose tissues such as in the liver (intra-hepatic lipids, IHCL) and within the muscle fibers (intramyocellular lipids, IMCL), are positively associated with obesity and insulin resistance. Furthermore, the accumulation of intracellular lipids is often cited as being a key determinant in the underlying mechanisms of insulin resistance. In addition of playing an important role in obesity and type 2 diabetes, these ectopic fat depositions are also observed in common conditions such as aging and physical inactivity. Paradoxically, regular physical activity (i.e. exercise training) inverses this association reducing insulin resistance while increasing IMCL. This situation lead to the hypothesis that these ectopic fat depositions do not directly affect insulin action, but that their deleterious effects depend on their stagnation (i.e. poor mobilization) and the accumulation of potentially damaging lipid metabolites, namely diacylglycerols and ceramides. It is not yet clear whether exercise induces remodeling of these ectopic lipid depots; thus the improvements in insulin resistance may be due to the effect of exercise on substrate utilization (by enhancing the capacity of lipid oxidation) or in the reduced formation of specific damaging fatty acid metabolites. Our intervention trial will test in skeletal muscle, liver and heart of obese, insulin-resistant older subjects the overall hypotheses that exercise improvement of fat oxidation capacity and/or decrease of damaging fat metabolites is a primary factor that predicts the improvement in insulin resistance. We utilize novel magnetic resonance techniques, histochemical and biochemical approaches to quantify changes in lipid and oxidative capacity before and after four months of exercise training. These changes will be measured in conjunction with in vivo measures of insulin resistance and fat oxidation. This project will provide novel and integrative information concerning mechanisms by which exercise, by enhancing the capacity of oxidative metabolism of fatty acids and/or decreasing the formation of damaging fat metabolites, can improves insulin resistance in older adults who are at high risk for the development of type 2 diabetes. Ultimately a better understanding of the mechanisms might help to identify therapeutic targets implicated in this metabolic dysregulation. Furthermore, the relationship between two organ specific fat depositions, i.e. the liver (“fatty liver”) and the heart (“fatty heart”), and insulin resistance before and after exercise training will be explored in older subjects with and without obesity. This is of significance as ICL might provide an important link between insulin resistance, obesity, type 2 diabetes and cardiovascular disease. This follow up proposal will allow finishing in good conditions this ambitious translational study. Implementing clinical research is a very intensive task and requires a strong synergistic setting, not only among the collaborators directly involved but also with the structural environment, namely with the different hospital services (Clinical Research Center, Sports Medicine Center, Radiology, Central labs). Some of the delays taken in the first years were not foreseeable, but we are now in excellent conditions to bring to finish this promising study and bring it to fruition.