Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.

Abstract

AIMS/HYPOTHESIS:

Although the substitution of saturated fatty acids with oleate has been recommended in the management of type 2 diabetes mellitus, the mechanisms by which oleate improves insulin resistance in skeletal muscle cells are not completely known. Here, we examined whether oleate, through activation of AMP-activated protein kinase (AMPK), prevented palmitate-induced endoplasmic reticulum (ER) stress, which is involved in the link between lipid-induced inflammation and insulin resistance.

METHODS:

Studies were conducted in mouse C2C12 myotubes and in the human myogenic cell line LHCN-M2. To analyse the involvement of AMPK, activators and inhibitors of this kinase and overexpression of a dominant negative AMPK construct (K45R) were used.

RESULTS:

Palmitate increased the levels of ER stress markers, whereas oleate did not. In palmitate-exposed cells incubated with a lower concentration of oleate, the effects of palmitate were prevented. The induction of ER stress markers by palmitate was prevented by the presence of the AMPK activators AICAR and A-769662. Moreover, the ability of oleate to prevent palmitate-induced ER stress and inflammation (nuclear factor-kappa B [NF-κB] DNA-binding activity and expression and secretion of IL6) as well as insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake was reversed in the presence of the AMPK inhibitor compound C or by overexpression of a dominant negative AMPK construct. Finally, palmitate reduced phospho-AMPK levels, whereas this was not observed in oleate-exposed cells or in palmitate-exposed cells supplemented with oleate.

CONCLUSIONS/INTERPRETATION:

Overall, these findings indicate that oleate prevents ER stress, inflammation and insulin resistance in palmitate-exposed skeletal muscle cells by activating AMPK.

• Authors: L Salvadó, T Coll, A M Gómez-Foix, E Salmerón, E Barroso, X Palomer, M Vázquez-Carrera
• Journal: Diabetologia (Diabetologia) Vol. 56 Issue 6 Pg. 1372-82 (Jun 2013) ISSN: 1432-0428 [Electronic] Germany
• PMID: 23460021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• Lipids
• NF-kappa B
• Pyrones
• Ribonucleotides
• Thiophenes
• Oleic Acid
• Palmitic Acid
• Aminoimidazole Carboxamide
• Adenylate Kinase
• AICA ribonucleotide
• 4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile

Topics

• Adenylate Kinase (metabolism)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Animals
• Biphenyl Compounds
• Cell Line
• Cell Nucleus (metabolism)
• Chromatography, High Pressure Liquid
• Endoplasmic Reticulum (drug effects, metabolism)
• Humans
• Inflammation (metabolism)
• Insulin Resistance
• Lipids (chemistry)
• Mice
• Muscle Cells (metabolism)
• Muscle, Skeletal (cytology)
• NF-kappa B (metabolism)
• Oleic Acid (pharmacology)
• Palmitic Acid (adverse effects, pharmacology)
• Pyrones (pharmacology)
• Ribonucleotides (pharmacology)
• Signal Transduction
• Thiophenes (pharmacology)