Research Article Details
| Article ID: | A14730 |
| PMID: | 29268121 |
| Source: | J Nutr Biochem |
| Title: | Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat. |
| Abstract: | Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly developed impaired glucose clearance followed by a gradual improvement from week 8 to week 39. All groups had similar responses to insulin 40 weeks post diet initiation despite severe nonalcoholic steatohepatitis in SOD-fed mice. We conclude that age-related alterations in glucose regulation may occur in both lean and obese mice and are modulated by dietary fat as indicated by the sustained metabolic homeostasis observed in mice fed ω3-polyunsaturated fatty acids. |
| DOI: | 10.1016/j.jnutbio.2017.09.026 |
| 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 |
| 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 |
| 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 |
| D137 | Fish oil | Biological drug | DB13961 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D504 | Polyunsaturated Fatty Acids | Supplement | -- | -- | -- | Under clinical trials | Details |