liver/biliary system
N |
• no apparent differences in steatosis, hepatomegaly, liver triglyceride levels, liver glycogen levels, or markers of inflammation when fed a high fat diet compared to diet matched controls
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• primary hepatocytes cultured in glucose free medium accumulate only 50 uM glucose in the medium compared to ~125 uM for controls
• expression of genes related to gluconeogenesis is low in primary hepatocytes related to controls and fails to increase in response to glucagon treatment
• labeled-metabolite analysis indicates that the impairment is primarily due to suppressed conversion of oxalacetate to PEP and downstream metabolites
• glucagon induced increase in cAMP levels is impaired and addition of a cell permeable cAMP derivative increases expression of gluconeogenesis related genes
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homeostasis/metabolism
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• on a high-fat diet mice do not display the expected increase in fasting glucose levels seen in diet matched controls
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• primary hepatocytes cultured in glucose free medium accumulate only 50 uM glucose in the medium compared to ~125 uM for controls
• expression of genes related to gluconeogenesis is low in primary hepatocytes related to controls and fails to increase in response to glucagon treatment
• labeled-metabolite analysis indicates that the impairment is primarily due to suppressed conversion of oxalacetate to PEP and downstream metabolites
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• in mice on a high-fat diet compared to diet matched controls
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• glucose tolerance test indicate a partial protection from high-fat diet induced diabetes
• however, high-fat diet induced increase in postprandial insulin levels is similar to diet matched controls
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