Research Article Details
| Article ID: | A00140 |
| PMID: | 35212643 |
| Source: | Eur J Endocrinol |
| Title: | Increased liver fat associates with severe metabolic perturbations in low birth weight men. |
| Abstract: | OBJECTIVE: Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of Type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW associates with severity of dysmetabolic traits, and finally whether such associations may be confounded by genetic factors. METHODS: Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from GWAS data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). RESULTS: The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P=0.014), and 20% of LBW versus no controls, had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD. Genetic risk for selected differential traits did not differ between groups. CONCLUSION: Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner. |
| DOI: | 10.1530/EJE-21-1221 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| 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 |