Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 308, Issue 9, Pages E756-E769Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00362.2014
Keywords
obesity; type 2 diabetes; adipocytes; macrophages; inflammation; fatty acid oxidation; CPT1
Categories
Funding
- Spanish Ministry of Science and Innovation [SAF2010-20039, SAF2013-45887-R, SAF2011-30520-C02-01, PI11/00085, SAF2012-33014, SAF2012-36186, SAF2012-30708, SAF2011-23626]
- CIBER Fisiopatologia de la Obesidad y la Nutricion [CB06/03/0001]
- CIBER Diabetes y Enfermedades Metabolicas Asociadas [CB07/08/0003]
- Instituto de Salud Carlos III
- European Union [FP7-277713]
- European Foundation for the Study of Diabetes (EFSD)/Lilly fellowship
- EFSD/Janssen-Rising Star research fellowship
- L'Oreal-UNESCO For Women in Science research fellowship
- Fondo de Investigacion Sanitaria [CP10/00438]
- European Regional Development Fund
- Ciencia sem Fronteiras-CNPq [237976/2012-9]
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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 CAR Delta 1 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.
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