Research Article Details
| Article ID: | A02348 |
| PMID: | 34407548 |
| Source: | Exp Clin Endocrinol Diabetes |
| Title: | Hepatic Meteorin-like and Krüppel-like Factor 3 are Associated with Weight Loss and Liver Injury. |
| Abstract: | OBJECTIVE: Laparoscopic adjustable gastric banding (LAGB) was found to be effective in reducing body weight and improving insulin resistance in patients with obesity and non-alcoholic fatty liver disease (NAFLD). The adipokine/myokine meteorin-like (METNRL) is an important regulator of whole-body energy expenditure. Krüppel-like factor 3 (KLF3), a regulator of METRNL expression in eosinophils, inhibits the beiging of adipose tissue in mice and therefore regulates adipose tissue development. METHODS: Thirty-three obese patients undergoing LAGB were included in the study. The hepatic and adipose tissue expression of METNRL and KLF3 was determined before (t0) and 6 months after (t6) LABG. The human liver cancer cell line (HepG2) was stimulated with cytokines and fatty acids and METNRL and KLF3 expressions were analyzed. RESULTS: LAGB-associated weight loss was correlated with decreased hepatic METNRL expression. The expression of METNRL and KLF3 in hepatic-and adipose tissues correlated before and after LAGB. Individuals with augmented LAGB-induced weight loss (>20 kg) showed lower hepatic METNRL and KLF3 expression before and after LAGB than patients with <20 kg weight loss. METNRL and KLF3 levels were higher in patients with higher NAFLD activity scores. HepG2 stimulation with interleukin-1β, tumor necrosis factor-α, palmitic acid but not interleukin-6, oleic acid, or lipopolysaccharide, induced the expression of one or both investigated adipokines. CONCLUSIONS: The novel description of METRNL and KLF3 as hepatokines could pave the way to target their production and/or signaling in obesity, NAFLD, and related disorders. Both proteins may act as possible biomarkers to estimate weight loss after bariatric surgery. |
| DOI: | 10.1055/a-1537-8950 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |
| S09 | Bariatric surgery | Metabolic surgery | -- | -- | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | 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 |