MiPsummer Programme pdf - Mitochondrial Physiology Society

75
Abstract # 43
Metabolic flexibility before and after lifestyle intervention in a diet-induced type 2 diabetes
animal model
Gonzalez-Franquesa, A 1 . Martinez-Navarro 1 , L. Fernandez-Ruiz, R 2 . Garcia-Roves, PM 1,2 .
1 Diabetes and Obesity Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS),
Barcelona, Spain. 2 Spanish Biomedical Research Centre in Diabetes and Associated Metabolic
Disorders (CIBERDEM).
Background
Sedentary habits along with an excess of macronutrients intake are spreading obesity-related type 2
diabetes hence, becoming an epidemic global problem. Metabolic flexibility (1) 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.
Objective
The aim of this project is to assess the metabolic adaptations on an animal model of diet-induced
type II diabetes and the effect of a lifestyle intervention programme in reverting them.
Methods
C57BL/6J male mice were used for the study and divided in three 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.
Results
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 II diabetic-like state. This communication
will be presenting how mitochondrial function will be responding to the different experimental
conditions. Mitochondrial function is being evaluated in liver, hypothalamus, glycolytic and
oxidative skeletal muscle, and white and brown adipose tissue.
Conclusion
At this point of the study, we have defined the phenotype of the three experimental groups;
demonstrated that our lifestyle intervention is able to re-establish glucose homeostasis and body
composition; and finally, performed mitochondrial function studies in key metabolic tissues.
References
(1)
Storlien L, Oakes ND, Kelley DE. Metabolic flexibility. Proc Nutr Soc. 2004;63(2):363-8.