Interleukin-1α deficiency reduces adiposity, glucose intolerance and hepatic de-novo lipogenesis in diet-induced obese mice
| Autor: | Alicia Leikin Frenkel, Yaniv Lustig, Aviv Shaish, Gadi Shlomai, Yehuda Kamari, Tal Almog, Roni Apte, Hana Levkovich, Michal Kandel Kfir, Iris Barshack, Ayelet Harari, Rinke Stienstra, Dror Harats, Yoram Bujanover |
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| Rok vydání: | 2019 |
| Předmět: |
Male
obesity Endocrinology Diabetes and Metabolism medicine.medical_treatment Mice Obese Mice Voeding Metabolisme en Genomica chemistry.chemical_compound 0302 clinical medicine Interleukin-1alpha Adipocyte Medicine Adiposity Mice Knockout 0303 health sciences Glucose tolerance test medicine.diagnostic_test Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Metabolism and Genomics Liver Metabolisme en Genomica 030220 oncology & carcinogenesis Lipogenesis Nutrition Metabolism and Genomics Obesity Studies medicine.medical_specialty Diet High-Fat 03 medical and health sciences Insulin resistance Voeding Internal medicine Animals Nutrition 030304 developmental biology Triglyceride Adiponectin business.industry Insulin Glucose Tolerance Test medicine.disease Fatty Liver de novo lipogenesis Endocrinology glucose intolerance chemistry Insulin Resistance business Diet-induced obese interleukin-1 |
| Zdroj: | BMJ Open Diabetes Research and Care, 7(1) BMJ Open Diabetes Research & Care BMJ Open Diabetes Research & Care, 7, e000650 BMJ Open Diabetes Research & Care, 7, 1, pp. e000650 BMJ Open Diabetes Research and Care 7 (2019) 1 |
| ISSN: | 2052-4897 |
| DOI: | 10.1136/bmjdrc-2019-000650 |
| Popis: | ObjectiveWhile extensive research revealed that interleukin (IL)-1β contributes to insulin resistance (IR) development, the role of IL-1α in obesity and IR was scarcely studied. Using control, whole body IL-1α knockout (KO) or myeloid-cell-specific IL-1α-deficient mice, we tested the hypothesis that IL-1α deficiency would protect against high-fat diet (HFD)-induced obesity and its metabolic consequences.Research design and methodsTo induce obesity and IR, control and IL-1α KO mice were given either chow or HFD for 16 weeks. Glucose tolerance test was performed at 10 and 15 weeks, representing early and progressive stages of glucose intolerance, respectively. Liver and epididymal white adipose tissue (eWAT) samples were analyzed for general morphology and adipocyte size. Plasma levels of adiponectin, insulin, total cholesterol and triglyceride (TG), lipoprotein profile as well as hepatic lipids were analyzed. Expression of lipid and inflammation-related genes in liver and eWAT was analyzed. Primary mouse hepatocytes isolated from control mice were treated either with dimethyl sulfoxide (DMSO) (control) or 20 ng/mL recombinant IL-1α for 24 hours and subjected to gene expression analysis.ResultsAlthough total body weight gain was similar, IL-1α KO mice showed reduced adiposity and were completely protected from HFD-induced glucose intolerance. In addition, plasma total cholesterol and TG levels were lower and HFD-induced accumulation of liver TGs was completely inhibited in IL-1α KO compared with control mice. Expression of stearoyl-CoA desaturase1 (SCD1), fatty acid synthase (FASN), elongation of long-chain fatty acids family member 6 (ELOVL6), acetyl-CoA carboxylase (ACC), key enzymes that promote de-novo lipogenesis, was lower in livers of IL-1α KO mice. Treatment with recombinant IL-1α elevated the expression of ELOVL6 and FASN in mouse primary hepatocytes. Finally, mice with myeloid-cell-specific deletion of IL-1α did not show reduced adiposity and improved glucose tolerance.ConclusionsWe demonstrate a novel role of IL-1α in promoting adiposity, obesity-induced glucose intolerance and liver TG accumulation and suggest that IL-1α blockade could be used for treatment of obesity and its metabolic consequences. |
| Databáze: | OpenAIRE |
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