Oleic Acid Protects Against Insulin Resistance by Regulating the Genes Related to the PI3K Signaling Pathway

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Aug 19

PMID 32806641

Citations 11

Authors

Carlos Lopez-Gomez

Concepcion Santiago-Fernandez

Sara Garcia-Serrano

Eva Garcia-Escobar

Carolina Gutierrez-Repiso

Cristina Rodriguez-Diaz

Ailec Ho-Plagaro

Flores Martin-Reyes

Lourdes Garrido-Sanchez

Sergio Valdes

Alberto Rodriguez-Canete

Francisca Rodriguez-Pacheco

Eduardo Garcia-Fuentes

Affiliations

Soon will be listed here.

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.

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References

AlKhateeb H, Qnais E . Preventive effect of oleate on palmitate-induced insulin resistance in skeletal muscle and its mechanism of action. J Physiol Biochem. 2017; 73(4):605-612. DOI: 10.1007/s13105-017-0594-9. View

Feng X, Wang T, Leng J, Chen Y, Liu J, Liu Y . Palmitate contributes to insulin resistance through downregulation of the Src-mediated phosphorylation of Akt in C2C12 myotubes. Biosci Biotechnol Biochem. 2012; 76(7):1356-61. DOI: 10.1271/bbb.120107. View

Lepretti M, Martucciello S, Burgos Aceves M, Putti R, Lionetti L . Omega-3 Fatty Acids and Insulin Resistance: Focus on the Regulation of Mitochondria and Endoplasmic Reticulum Stress. Nutrients. 2018; 10(3). PMC: 5872768. DOI: 10.3390/nu10030350. View

Schmitz-Peiffer C, Craig D, Biden T . Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem. 1999; 274(34):24202-10. DOI: 10.1074/jbc.274.34.24202. View

Piro S, Maniscalchi E, Monello A, Pandini G, Mascali L, Rabuazzo A . Palmitate affects insulin receptor phosphorylation and intracellular insulin signal in a pancreatic alpha-cell line. Endocrinology. 2010; 151(9):4197-206. DOI: 10.1210/en.2009-1472. View

Rodriguez-Pacheco F, Gutierrez-Repiso C, Garcia-Serrano S, Alaminos-Castillo M, Ho-Plagaro A, Valdes S . The pro-/anti-inflammatory effects of different fatty acids on visceral adipocytes are partially mediated by GPR120. Eur J Nutr. 2016; 56(4):1743-1752. DOI: 10.1007/s00394-016-1222-0. View

Nelson V, Jiang Y, Dickman K, Ballou L, Lin R . Adipose tissue insulin resistance due to loss of PI3K p110α leads to decreased energy expenditure and obesity. Am J Physiol Endocrinol Metab. 2014; 306(10):E1205-16. PMC: 4025064. DOI: 10.1152/ajpendo.00625.2013. View

Mauvais-Jarvis F, Ueki K, Fruman D, Hirshman M, Sakamoto K, Goodyear L . Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest. 2002; 109(1):141-9. PMC: 150818. DOI: 10.1172/JCI13305. View

Asano T, Fujishiro M, Kushiyama A, Nakatsu Y, Yoneda M, Kamata H . Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. Biol Pharm Bull. 2007; 30(9):1610-6. DOI: 10.1248/bpb.30.1610. View

10.

Riccardi G, Giacco R, Rivellese A . Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr. 2004; 23(4):447-56. DOI: 10.1016/j.clnu.2004.02.006. View

11.

Karpe F, Dickmann J, Frayn K . Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 2011; 60(10):2441-9. PMC: 3178283. DOI: 10.2337/db11-0425. View

12.

Bandyopadhyay G, Yu J, Ofrecio J, Olefsky J . Increased p85/55/50 expression and decreased phosphotidylinositol 3-kinase activity in insulin-resistant human skeletal muscle. Diabetes. 2005; 54(8):2351-9. DOI: 10.2337/diabetes.54.8.2351. View

13.

Boden G, Chen X, Ruiz J, White J, Rossetti L . Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest. 1994; 93(6):2438-46. PMC: 294452. DOI: 10.1172/JCI117252. View

14.

Draznin B . Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin. Diabetes. 2006; 55(8):2392-7. DOI: 10.2337/db06-0391. View

15.

Bikman B, Zheng D, Reed M, Hickner R, Houmard J, Dohm G . Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment. Am J Physiol Regul Integr Comp Physiol. 2010; 298(6):R1692-9. PMC: 2886707. DOI: 10.1152/ajpregu.00190.2009. View

16.

Palomer X, Pizarro-Delgado J, Barroso E, Vazquez-Carrera M . Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus. Trends Endocrinol Metab. 2018; 29(3):178-190. DOI: 10.1016/j.tem.2017.11.009. View

17.

Araki E, Lipes M, Patti M, Bruning J, Haag 3rd B, Johnson R . Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature. 1994; 372(6502):186-90. DOI: 10.1038/372186a0. View

18.

Weir N, Nomura S, Steffen B, Guan W, Karger A, Klein R . Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis. Clin Nutr. 2020; 39(10):3031-3041. PMC: 7374052. DOI: 10.1016/j.clnu.2020.01.003. View

19.

Fritsche L, Weigert C, Haring H, Lehmann R . How insulin receptor substrate proteins regulate the metabolic capacity of the liver--implications for health and disease. Curr Med Chem. 2008; 15(13):1316-29. DOI: 10.2174/092986708784534956. View

20.

Barbarroja N, Lopez-Pedrera R, Mayas M, Garcia-Fuentes E, Garrido-Sanchez L, Macias-Gonzalez M . The obese healthy paradox: is inflammation the answer?. Biochem J. 2010; 430(1):141-9. DOI: 10.1042/BJ20100285. View