López-Gómez Carlos, Santiago-Fernández Concepción, García-Serrano Sara, García-Escobar Eva, Gutiérrez-Repiso Carolina, Rodríguez-Díaz Cristina, Ho-Plágaro Ailec, Martín-Reyes Flores, Garrido-Sánchez Lourdes, Valdés Sergio, Rodríguez-Cañete Alberto, Rodríguez-Pacheco Francisca, García-Fuentes Eduardo
Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria/Instituto de Investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.
Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga/Instituto de Investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.
J Clin Med. 2020 Aug 12;9(8):2615. doi: 10.3390/jcm9082615.
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.
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.
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.
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.
不同类型脂肪酸对胰岛素受体底物1（IRS1）/磷脂酰肌醇-3激酶（PI3K）信号通路关键分子基因表达的影响鲜有研究。
我们分析了病态肥胖患者和非肥胖患者内脏脂肪组织中IRS1、p85α和p110β的mRNA表达以及磷脂的脂肪酸组成。此外，我们还分析了用油酸、亚油酸、棕榈酸和二十二碳六烯酸孵育的内脏脂肪细胞中这些基因的表达。
我们发现病态肥胖患者中IRS1表达降低，且与胰岛素抵抗无关；胰岛素抵抗较低的患者中p110β表达降低。p85α与硬脂酸之间、IRS1与p110β与棕榈酸和二十二碳六烯酸之间呈正相关。相反，p85α与油酸之间、IRS1与p110β与亚油酸、花生四烯酸和肾上腺酸之间呈负相关。用棕榈酸孵育会降低IRS1表达。用油酸和二十二碳六烯酸孵育后p85α下调，用棕榈酸孵育后上调。用油酸和棕榈酸孵育后p110β表达分别增加和降低。油酸和二十二碳六烯酸使p85α/p110β比值降低，棕榈酸使其升高。
我们的体外研究结果表明，棕榈酸对胰岛素信号通路相关基因的表达具有有害作用，而油酸具有更高且更有益的作用。二十二碳六烯酸有轻微的有益作用。脂肪酸诱导的与IRS1/PI3K通路相关基因的调节可能是脂肪酸调节内脏脂肪细胞胰岛素敏感性的一种新机制。
