PMID- 25714670 OWN - NLM STAT- MEDLINE DCOM- 20150803 LR - 20150502 IS - 1522-1555 (Electronic) IS - 0193-1849 (Linking) VI - 308 IP - 9 DP - 2015 May 1 TI - Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. PG - E756-69 LID - 10.1152/ajpendo.00362.2014 [doi] AB - Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARDelta1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes. CI - Copyright (c) 2015 the American Physiological Society. FAU - Malandrino, Maria Ida AU - Malandrino MI AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Fucho, Raquel AU - Fucho R AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Weber, Mineia AU - Weber M AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Calderon-Dominguez, Maria AU - Calderon-Dominguez M AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Mir, Joan Francesc AU - Mir JF AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Valcarcel, Lorea AU - Valcarcel L AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Escote, Xavier AU - Escote X AD - Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigacio Sanitaria Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; FAU - Gomez-Serrano, Maria AU - Gomez-Serrano M AD - Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, Madrid, Spain; FAU - Peral, Belen AU - Peral B AD - Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, Madrid, Spain; FAU - Salvado, Laia AU - Salvado L AD - Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry and Institut de Biomedicina de la Universitat de Barcelona, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; and. FAU - Fernandez-Veledo, Sonia AU - Fernandez-Veledo S AD - Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigacio Sanitaria Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; FAU - Casals, Nuria AU - Casals N AD - Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain. FAU - Vazquez-Carrera, Manuel AU - Vazquez-Carrera M AD - Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry and Institut de Biomedicina de la Universitat de Barcelona, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; and. FAU - Villarroya, Francesc AU - Villarroya F AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Vendrell, Joan J AU - Vendrell JJ AD - Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigacio Sanitaria Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabolicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; FAU - Serra, Dolors AU - Serra D AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; FAU - Herrero, Laura AU - Herrero L AD - Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatologia de la Obesidad y la Nutricion, Instituto de Salud Carlos III, Madrid, Spain; lherrero@ub.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150224 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Fatty Acids) RN - 0 (Lipids) RN - 0 (Triglycerides) SB - IM EIN - Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E795. PMID: 27140962 MH - 3T3-L1 Cells MH - Adipocytes/*metabolism MH - Adult MH - Aged MH - Animals MH - Cohort Studies MH - Diabetes Mellitus, Type 2/metabolism MH - Fatty Acids/*metabolism MH - Female MH - Humans MH - Inflammation/*metabolism MH - Lipid Metabolism/*drug effects MH - Lipids/*pharmacology MH - Macrophages/*metabolism MH - Male MH - Mice MH - Middle Aged MH - Obesity/metabolism MH - Oxidation-Reduction MH - Triglycerides/metabolism OTO - NOTNLM OT - CPT1 OT - adipocytes OT - fatty acid oxidation OT - inflammation OT - macrophages OT - obesity OT - type 2 diabetes EDAT- 2015/02/26 06:00 MHDA- 2015/08/04 06:00 CRDT- 2015/02/26 06:00 PHST- 2014/07/30 00:00 [received] PHST- 2015/02/19 00:00 [accepted] PHST- 2015/02/26 06:00 [entrez] PHST- 2015/02/26 06:00 [pubmed] PHST- 2015/08/04 06:00 [medline] AID - ajpendo.00362.2014 [pii] AID - 10.1152/ajpendo.00362.2014 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2015 May 1;308(9):E756-69. doi: 10.1152/ajpendo.00362.2014. Epub 2015 Feb 24.