Linoleate Appears to Protect Against Palmitate-induced Inflammation in Huh7 Cells

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2014 Jun 3

PMID 24885871

Citations 7

Authors

Hitoshi Maruyama

Masanori Takahashi

Tadashi Sekimoto

Taro Shimada

Osamu Yokosuka

Affiliations

Soon will be listed here.

Abstract

Background: Polyunsaturated fatty acids (PUFAs) may protect against metabolic diseases. Although the benefits of the n-3 family of PUFA have been well investigated in nonalcoholic steatohepatitis (NASH), little is known about the effect of the n-6 family. This study examined the effect of linoleate, a member of the n-6 family, on regulation of the palmitate-induced inflammatory cytokine interleukin-8 (IL8) in hepatocytes.

Methods: Huh7 cells and HepG2 cells were cultured with and without free fatty acid treatment (palmitate and linoleate, alone or in combination, 100-1000 μM). Inflammatory pathways, lipid accumulation, apoptosis and cell viability were monitored.

Results: Dose- and time-related changes of IL8 mRNA expression were examined and 9 h treatment with 500 μM palmitate showed the greatest elevation of IL8. Co-treatment with 500 μM palmitate and 400 μM linoleate significantly suppressed IL8 production below that with palmitate alone in both cells (both mRNA and protein). A quantitative measurement for lipid accumulation showed no significant difference between palmitate-treated cells (1.69 ± 0.21), linoleate-treated cells (1.61 ± 0.16) and palmitate and linoleate-treated cells (1.73 ± 0.22, NS, n = 7). The co-treatment with 400 μM linoleate inhibited phospho-c-Jun N-terminal kinase (pJNK) activation and IkBα reduction caused by 500 μM palmitate treatment. Treatment with 400 μM linoleate alone led to IL8 production (5.48 fold change), similar to co-treatment, with no influence on the expression of pJNK/IkBα. The cell viability was similar between treatment with 500 μM palmitate and with both 500 μM palmitate and 400 μM linoleate, showing no significant changes in the expression of cleaved caspase-3.

Conclusions: Linoleate is a potent regulator of the proinflammatory cytokine IL8 via the JNK and nuclear factor kappa B pathways that are involved in the pathophysiology of NASH, suggesting a future recommendation of dietary management.

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References

Szabo G, Velayudham A, Romics Jr L, Mandrekar P . Modulation of non-alcoholic steatohepatitis by pattern recognition receptors in mice: the role of toll-like receptors 2 and 4. Alcohol Clin Exp Res. 2005; 29(11 Suppl):140S-145S. DOI: 10.1097/01.alc.0000189287.83544.33. View

Farrell G, Larter C . Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006; 43(2 Suppl 1):S99-S112. DOI: 10.1002/hep.20973. View

Clarke S . Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr. 2001; 131(4):1129-32. DOI: 10.1093/jn/131.4.1129. View

Sanyal A, Mirshahi F, Rizzo W, Contos M, Sterling R, Luketic V . Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001; 120(5):1183-92. DOI: 10.1053/gast.2001.23256. View

Wilson M, Blake W, Salati L, Clarke S . Potency of polyunsaturated and saturated fats as short-term inhibitors of hepatic lipogenesis in rats. J Nutr. 1990; 120(6):544-52. DOI: 10.1093/jn/120.6.544. View

Day C, James O . Steatohepatitis: a tale of two "hits"?. Gastroenterology. 1998; 114(4):842-5. DOI: 10.1016/s0016-5085(98)70599-2. View

Feldstein A, Werneburg N, Canbay A, Guicciardi M, Bronk S, Rydzewski R . Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology. 2004; 40(1):185-94. DOI: 10.1002/hep.20283. View

Ricchi M, Odoardi M, Carulli L, Anzivino C, Ballestri S, Pinetti A . Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol. 2009; 24(5):830-40. DOI: 10.1111/j.1440-1746.2008.05733.x. View

Nichols P, Kitessa S, Abeywardena M . Commentary on a trial comparing krill oil versus fish oil. Lipids Health Dis. 2014; 13:2. PMC: 3881490. DOI: 10.1186/1476-511X-13-2. View

10.

Lhomme L, Esser N, Riva L, Scheen A, Paquot N, Piette J . Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages. J Lipid Res. 2013; 54(11):2998-3008. PMC: 3793604. DOI: 10.1194/jlr.M037861. View

11.

Chalasani N, Younossi Z, Lavine J, Diehl A, Brunt E, Cusi K . The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012; 142(7):1592-609. DOI: 10.1053/j.gastro.2012.04.001. View

12.

Donnelly K, Smith C, Schwarzenberg S, Jessurun J, Boldt M, Parks E . Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115(5):1343-51. PMC: 1087172. DOI: 10.1172/JCI23621. View

13.

Wei Y, Wang D, Gentile C, Pagliassotti M . Reduced endoplasmic reticulum luminal calcium links saturated fatty acid-mediated endoplasmic reticulum stress and cell death in liver cells. Mol Cell Biochem. 2009; 331(1-2):31-40. PMC: 2899892. DOI: 10.1007/s11010-009-0142-1. View

14.

Harris W, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel L, Appel L . Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on.... Circulation. 2009; 119(6):902-7. DOI: 10.1161/CIRCULATIONAHA.108.191627. View

15.

Cortez-Pinto H, Carneiro de Moura M, Day C . Non-alcoholic steatohepatitis: from cell biology to clinical practice. J Hepatol. 2005; 44(1):197-208. DOI: 10.1016/j.jhep.2005.09.002. View

16.

Allard J, Aghdassi E, Mohammed S, Raman M, Avand G, Arendt B . Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study. J Hepatol. 2007; 48(2):300-7. DOI: 10.1016/j.jhep.2007.09.009. View

17.

James O, Day C . Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance. J Hepatol. 1998; 29(3):495-501. DOI: 10.1016/s0168-8278(98)80073-1. View

18.

Estep J, Baranova A, Hossain N, Elariny H, Ankrah K, Afendy A . Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis. Obes Surg. 2009; 19(5):617-24. DOI: 10.1007/s11695-009-9814-x. View

19.

Lee J, Cho H, Kwon Y . Palmitate induces insulin resistance without significant intracellular triglyceride accumulation in HepG2 cells. Metabolism. 2009; 59(7):927-34. DOI: 10.1016/j.metabol.2009.10.012. View

20.

Browning J, Szczepaniak L, Dobbins R, Nuremberg P, Horton J, Cohen J . Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004; 40(6):1387-95. DOI: 10.1002/hep.20466. View