Research Article Details
| Article ID: | A09361 |
| PMID: | 31777896 |
| Source: | Food Funct |
| Title: | Attenuation of metabolic syndrome in the ob/ob mouse model by resistant starch intervention is dose dependent. |
| Abstract: | The current study applied an ob/ob mouse model of obesity for investigating the impact of different RS doses in a high-fat (HF) diet on the attenuation of metabolic syndrome. Although a significant reduction of body weight was not achieved, RS intervention significantly decreased liver weight with suppressed lipid accumulation in the liver tissue and reduced adipocyte size in the fat tissue. All levels of RS intervention were associated with significantly enriched pathways for PPAR, NAFLD and cGMP-PKG signaling. In contrast, either a medium or a higher RS intake (MRS and HRS, respectively) led the AMPK signaling pathway to be significantly enriched but not a diet with lower RS intake. More importantly, sphingolipid biosynthesis activity was noted with MRS and HRS intervention, which is highly associated with the improvement in insulin resistance, and the pathway of type II diabetes mellitus was correspondingly significantly enriched in the HRS group, demonstrating a dose-dependent manner. Similarly, there was no significant difference in the ratio of Bacteroidetes and Firmicutes between high-fat diet and RS groups until RS reached a certain level (i.e. in the HRS group). Furthermore, increased profiles of both Prevotellaceae and Coriobacteriaceae in the HF group were noted for the first time with a revised function from RS intervention, which is consistent with the content of lipopolysaccharides in their corresponding serum. Gut microbiota functional analysis showed that primary and secondary bile acid biosynthesis was also noted to be enriched following the RS intervention, benefiting cholesterol homeostasis. This study further highlights the association of RS consumption with the attenuation of metabolic syndrome in an obesity model, and its functionality is characterized by dose-dependence. |
| DOI: | 10.1039/c9fo01771b |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |