Metabolism
High dietary fat and sucrose result in an extensive and time-dependent deterioration in health of multiple physiological systems in mice
Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD).Metabolomic analysis of insulin resistance across different mouse strains and diets
Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high-fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle.Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway
Background: Insulin regulates metabolism via the PI3K/Akt pathway.Results: A kinome siRNA screen identified PFKFB3, a glycolysis regulator, as a modulator of insulin action. Manipulation of PFKFB3 activity or glycolysis affected insulin signaling.Conclusion: Intracellular metabolism modulates important signal transduction pathways.Significance: The novel link between glycolysis and growth factor signaling has important implications for the treatment of metabolic diseases.
