Abstract
Background: The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied. Material and Methods: We analyzed IRS1, p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.
Highlights
Insulin resistance (IR) is a common complication in obesity and leads to the development of the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM)
The main result of this study was the different effect observed in the incubations with different types of fatty acids on the expression of genes involved in IRS1/phosphatidylinositol 3 kinase (PI3K) pathway in visceral adipocytes
We observed a down-regulation of IRS1 and an increased p85α/p110β ratio with palmitic acid
Summary
Insulin resistance (IR) is a common complication in obesity and leads to the development of the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM). Two mechanisms involving this pathway have emerged as being mainly responsible for the development of IR: Serine phosphorylation of IRS1 [6,7], and increased expression of p85α and alteration of the stoichiometry with p110β Both the pool of free p85α subunit and the heterodimer p85α/p110β compete for the binding sites of IRS proteins. We analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes
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