Garcia-Roves 2013 Abstract MiP2013
|Garcia-Roves PM, Gonzalez-Franquesa A, Martinez-Navarro L, Fernandez-Ruiz R (2013) Metabolic flexibility before and after lifestyle intervention in a diet-induced type 2 diabetes animal model. Mitochondr Physiol Network 18.08.|
Sedentary habits along with an excess of macronutrients intake are spreading obesity-related type 2 diabetes hence, becoming an epidemic global problem. Metabolic flexibility  is defined by Kelley et al. as the “clear capacity to utilize lipid and carbohydrate fuels and to transition between them”. The disruption of this ability, the so-called “metabolic inflexibility”, could play an important role during the early onset of type 2 diabetes when there is already evidence of fasting hyperinsulinemia, hyperglycemia and hyperleptinemia. Nowadays, there is still a controversy whether mitochondrial dysfunction plays a causative role on type 2 diabetes etiology [2,3,4]. Our current interest is to assess the metabolic adaptations occurring on an animal model of diet-induced type 2 diabetes and the effect of a lifestyle intervention programme in reverting them. For this purpose we are studying three different experimental groups: a control (Ctrl) group (fed for 16 weeks with chow standard diet), a high fat diet (HFD-pathological) group (fed for 16 weeks with 45% HFD) and an intervention (Int) group (in which a lifestyle intervention was performed after feeding the animals with 45% HFD for 16 weeks). This lifestyle intervention consisted of calorie restriction, modification of the 45% HFD with mono- and poly-unsaturated fatty acids, and exercise training for 5 weeks.
The mice in the HFD-pathological group were glucose intolerant and had disrupted insulin sensitivity when compared with their littermates, Ctrl group. Those HFD-pathological mice were overweight and hyperinsulinemic and hyperleptinemic after overnight fasting. Morphological analyses of the pancreas showed that the HFD-pathological mice had more and bigger pancreatic islets than the Ctrl littermate mice. Isolated islets from HFD-pathological mice had an increased in vitro glucose-stimulated insulin secretion. When the lifestyle intervention was performed in the HFD-pathological mice, the Int group mice reversed most of the phenotype previously defined for the HFD-pathological group mice and showed a general improvement in glucose homeostasis; thus, reversing the deleterious effects that led them to a type 2 diabetic-like state.
This communication will be presenting how mitochondrial function is modulated by the different experimental conditions. Mitochondrial function is being evaluated in liver, hypothalamus, glycolytic and oxidative skeletal muscle, and white and brown adipose tissues.
• Keywords: Obesity, Exercise, Hypothalamus
• O2k-Network Lab: ES Barcelona Garcia-Roves PM
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle, Nervous system, Liver, Islet cell;pancreas;thymus, Fat Preparation: Permeabilized cells, Permeabilized tissue, Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, CIV, NS HRR: Oxygraph-2k
1 - Diabetes and Obesity Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS);
2 - Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) Barcelona, Spain.
- Storlien L, Oakes ND, Kelley DE (2004) Metabolic flexibility. Proc Nutr Soc 63: 363-368.
- Lowell BB and Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307: 384-387.
- Holloszy JO (2013) "Deficiency" of mitochondria in muscle does not cause insulin resistance. Diabetes 62: 1036-1040.
- Goodpaster BH (2013) Mitochondrial deficiency is associated with insulin resistance. Diabetes 62: 1032-1035.