Research Article Details
| Article ID: | A19724 |
| PMID: | 26394261 |
| Source: | Appl Physiol Nutr Metab |
| Title: | Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats. |
| Abstract: | Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD is unclear. We assessed the effects of metformin, caloric restriction, and their combination on NAFLD in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (age 20 weeks; n = 6-8 per group) were fed ad libitum (AL), given metformin (300 mg·kg(-1)·day(-1); Met), calorically restricted (70% of AL; CR), or calorically restricted and given metformin (CR+Met) for 12 weeks. Met lowered adiposity compared with AL but not to the same magnitude as CR or CR+Met (p < 0.05). Although only CR improved fasting insulin and glucose, the combination of CR+Met was needed to improve post-challenge glucose tolerance. All treatments lowered hepatic triglycerides, but further improvements were observed in the CR groups (p < 0.05, Met vs. CR or CR+Met) and a further reduction in serum alanine aminotransferases was observed in CR+Met rats. CR lowered markers of hepatic de novo lipogenesis (fatty acid synthase, acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase-1 (SCD-1)) and increased hepatic mitochondrial activity (palmitate oxidation and β-hydroxyacyl CoA dehydrogenase (β-HAD) activity). Changes were enhanced in the CR+Met group for ACC, SCD-1, β-HAD, and the mitophagy marker BNIP3. Met decreased total hepatic mTOR content and inhibited mTOR complex 1, which may have contributed to Met-induced reductions in de novo lipogenesis. These findings in the OLETF rat suggest that the combination of caloric restriction and metformin may provide a more optimal approach than either treatment alone in the management of type 2 diabetes and NAFLD. |
| DOI: | 10.1139/apnm-2015-0236 |
| 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 |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | 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 | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |