Research Article Details
| Article ID: | A15611 |
| PMID: | 28811651 |
| Source: | Int J Obes (Lond) |
| Title: | iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner. |
| Abstract: | Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells. |
| DOI: | 10.1038/ijo.2017.200 |
| 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 |
| 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 |