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Interleukin-1α deficiency reduces adiposity, glucose intolerance and hepatic de-novo lipogenesis in diet-induced obese mice.
| Content Provider | Europe PMC |
|---|---|
| Author | Almog, Tal Kandel Kfir, Michal Levkovich, Hana Shlomai, Gadi Barshack, Iris Stienstra, Rinke Lustig, Yaniv Leikin Frenkel, Alicia Harari, Ayelet Bujanover, Yoram Apte, Roni Shaish, Aviv Harats, Dror Kamari, Yehuda |
| Copyright Year | 2019 |
| Abstract | 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. |
| Journal | BMJ Open Diabetes Research & Care |
| Volume Number | 7 |
| PubMed Central reference number | PMC6827792 |
| Issue Number | 1 |
| PubMed reference number | 31749969 |
| e-ISSN | 20524897 |
| DOI | 10.1136/bmjdrc-2019-000650 |
| Language | English |
| Publisher | BMJ Publishing Group |
| Publisher Date | 2019-10-17 |
| Publisher Place | BMA House, Tavistock Square, London, WC1H 9JR |
| Access Restriction | Open |
| Rights License | This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
| Subject Keyword | obesity glucose intolerance de novo lipogenesis interleukin-1 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism |
