Research Article Details
| Article ID: | A52972 |
| PMID: | 18596860 |
| Source: | Trans Am Clin Climatol Assoc |
| Title: | Fatty liver and insulin resistance: not always linked. |
| Abstract: | One significant clinical symptom of familial hypobetalipoproteinemia [FHBL] due to defects in apolipoprotein B (apoB) is steatohepatosis. However, the increased hepatic fat content in apoB-related FHBL subjects was not associated with glucose intolerance, in contrast with what is the case in the metabolic syndrome. Meanwhile, in human subjects with similar apoB truncations, degree of obesity and insulin sensitivity, their liver triglyceride (TG) contents may vary considerably, suggesting that, in addition to defective apoB, other genes may affect the magnitude of hepatic TG accumulation. We hypothesized that genetic background affects the severity of hepatic steatosis and the expression of insulin sensitivity. To test the hypotheses, mouse apoB38.9-bearing congenies were bred under high, medium and low liver triglyceride (TG) backgrounds using "speed congenics" approach. These mice were fed on regular diet for 12 weeks. Their insulin sensitivity, serum and liver lipids were assessed. The highest liver fat strain [BALB/cByJ] accumulated significantly higher TG in the liver under apoB38.9 heterozygous condition, while the lowest liver fat strain [SWR/J] had the smallest liver TG change, suggesting that the genetic backgrounds affected the hepatic TG responses to the presence of the apoB38.9 mutation. Interestingly, only the low liver fat strain [SWR/J-apoB38.9] showed significant upward shifts of both glucose tolerance test (GTT) and insulin tolerance test (ITT) curves. Neither the glucose nor the insulin tolerance curves were altered in the two cognate congenics with higher liver fat content [BALB/cByJ and C57BL/6J]. Thus, hepatic TG contents and measures of glucose metabolism were dissociated from each other. It is tempting to conclude that hepatic TG per se may not be responsible for the insulin resistance seen in fatty liver. The genetic/molecular bases for the differences between SWR/J and the other two strains with respect to their glucose metabolic responses to increases in hepatic TG contents remain to be elucidated. |
| DOI: |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |