PMID- 25899451 OWN - NLM STAT- MEDLINE DCOM- 20160310 LR - 20220321 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 58 IP - 7 DP - 2015 Jul TI - Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. PG - 1587-600 LID - 10.1007/s00125-015-3583-y [doi] AB - AIMS/HYPOTHESIS: Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood. METHODS: We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks. RESULTS: Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-alpha, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1beta [MuIP-1beta]), compared with sham-operated mice. Plasma IL-17 and MIP-1beta concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-alpha and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations. CONCLUSIONS/INTERPRETATION: Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice. FAU - Hocking, Samantha L AU - Hocking SL AD - Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, 2010, Sydney, NSW, Australia. FAU - Stewart, Rebecca L AU - Stewart RL FAU - Brandon, Amanda E AU - Brandon AE FAU - Suryana, Eurwin AU - Suryana E FAU - Stuart, Ella AU - Stuart E FAU - Baldwin, Emily M AU - Baldwin EM FAU - Kolumam, Ganesh A AU - Kolumam GA FAU - Modrusan, Zora AU - Modrusan Z FAU - Junutula, Jagath R AU - Junutula JR FAU - Gunton, Jenny E AU - Gunton JE FAU - Medynskyj, Michael AU - Medynskyj M FAU - Blaber, Sinead P AU - Blaber SP FAU - Karsten, Elisabeth AU - Karsten E FAU - Herbert, Benjamin R AU - Herbert BR FAU - James, David E AU - James DE FAU - Cooney, Gregory J AU - Cooney GJ FAU - Swarbrick, Michael M AU - Swarbrick MM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150422 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Adiponectin) RN - 0 (Cytokines) RN - 0 (Insulin) RN - 0 (Leptin) RN - 0 (Triglycerides) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adipocytes/metabolism/ultrastructure MH - Adiponectin/blood MH - Adiposity MH - Animals MH - Body Composition MH - Cytokines/blood MH - Diet, High-Fat/adverse effects MH - Eating MH - Gluconeogenesis MH - Glucose/metabolism MH - Glucose Intolerance/*surgery MH - Inflammation/*surgery MH - Insulin/blood MH - Leptin/blood MH - Liver/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Subcutaneous Fat/*transplantation MH - Triglycerides/metabolism EDAT- 2015/04/23 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/04/23 06:00 PHST- 2014/10/30 00:00 [received] PHST- 2015/03/13 00:00 [accepted] PHST- 2015/04/23 06:00 [entrez] PHST- 2015/04/23 06:00 [pubmed] PHST- 2016/03/11 06:00 [medline] AID - 10.1007/s00125-015-3583-y [doi] PST - ppublish SO - Diabetologia. 2015 Jul;58(7):1587-600. doi: 10.1007/s00125-015-3583-y. Epub 2015 Apr 22.