Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes

Aims To determine the presence and possible involvement of FAT/CD36, FABPpm and FATP‐2, transporters in (i) fatty acids movement across plasma membrane and (ii) an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in primary hepatocytes. Methods Primary hepatocytes were tre...

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Published in:	Acta Physiologica 2013-02, Vol.207 (2), p.346-357
Main Authors:	Chabowski, A., Żendzian-Piotrowska, M., Konstantynowicz, K., Pankiewicz, W., Mikłosz, A., Łukaszuk, B., Górski, J.
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Biological Transport Blotting, Western CD36 Antigens - metabolism ceramide Coenzyme A Ligases - metabolism diacylglycerols FAT/CD36 Fatty Acid Transport Proteins - metabolism Fatty Acid-Binding Proteins - metabolism Fatty acids Fundamental and applied biological sciences. Psychology Glucose GLUT hepatocytes Hepatocytes - metabolism Hepatocytes - pathology Hyperglycemia Insulin resistance Insulin Resistance - physiology Male Oleic Acid - metabolism Oleic Acid - toxicity Palmitates - metabolism Palmitates - toxicity Proteins Rats Rats, Wistar Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:	Aims To determine the presence and possible involvement of FAT/CD36, FABPpm and FATP‐2, transporters in (i) fatty acids movement across plasma membrane and (ii) an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in primary hepatocytes. Methods Primary hepatocytes were treated with either PA and OA or combination of activators (AICAR, Insulin) or inhibitors (SSO, phloretin) of FA transport. Expression of FA and glucose transporters as well as insulin signalling proteins was determined using Western blot analyses. Palmitate and glucose transport was measured using radioactive isotopes. Intracellular lipid content [ceramide, diacylglycerols (DG) and triacylglycerols] and FA composition were estimated by GLC. Results In primary hepatocytes, adding phloretin diminished insulin, and AICAR stimulated palmitate transport. Both PA and OA fatty acids induced the protein expression of FAT/CD36 and FATP‐2 with concomitant: (i) reduction in GLUT‐2 protein content, (ii) inhibition of insulin‐stimulated glucose uptake, (iii) reduction in insulin‐stimulated activation of AKT and GSK, (iv) accumulation of either DG (PA and OA) or ceramide (only PA). Conclusions FA transport into hepatocytes is, at least in part, protein‐mediated process, and both PA and OA induce the protein expression of FAT/CD36 and FATP‐2. Both saturated (PA) and unsaturated (OA) fatty acids induce insulin resistance in primary hepatocytes, associated with the accumulation of DG and/or ceramide.
ISSN:	1748-1708 1748-1716