Abstract
Studies have shown that not only does palmitic acid promote triglyceride (TG) accumulation, but it also affects cell viability in in vitro steatosis models. However, to what degree these effects are mediated by steatosis in goose primary hepatocytes is unknown. In this study, the effects of palmitic acid on the lipid metabolism homeostasis pathway and on apoptosis were determined. The authors measured the mRNA levels of genes involved in TG synthesis, lipid deposition, fatty acid oxidation and the assembly and secretion of VLDL–TG in goose primary hepatocytes. The results indicated that palmitic acid can significantly reduce the activity of goose hepatocytes, and that palmitic acid had a significant effect on TG accumulation; however, with increasing palmitic acid concentrations, the extracellular TG and extracellular VLDL concentration gradually decreased. With increasing palmitic acid concentrations, the gene expression levels of DGAT1, DGAT2, PPARα, CPT-1, FoxO1 and MTTP (which regulate hepatic TG synthesis, fatty acid oxidation and the assembly and secretion of VLDL–TGs) first increased and then decreased; the change in PLIN gene expression was palmitic acid dose-dependent, similar to the regulatory mode of intracellular TG accumulation. In conclusion, this study clearly shows that palmitic acid can promote TG accumulation and induce apoptosis in goose primary hepatocytes, and this effect may be related to the lipid metabolism pathway.
Similar content being viewed by others
Abbreviations
- VLDL:
-
Very low-density lipoprotein
- TG:
-
Triglyceride
- DGAT:
-
Acyl CoA:diacylglycerol acyltransferase
- MTTP:
-
Microsomal triglyceride transfer protein
- FoxO1:
-
Forkhead box O1
- PPARs:
-
Peroxisome proliferator-activated receptors
- PLIN:
-
Perilipin
References
Wei Y, Wang D, Pagliassotti MJ (2007) Saturated fatty acid-mediated endoplasmic reticulum stress and apoptosis are augmented by trans-10, cis-12-conjugated linoleic acid in liver cells. Mol Cell Biochem 303:105–113
Ji J, Zhang L, Wang P, Mu YM, Zhu XY, Wu YY, Yu H, Zhang B, Chen SM, Sun XZ (2005) Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes in culture. Exp Toxicol Pathol 56:369–376
Mourot J, Guy G, Lagarrigue S, Peiniau P, Hermier D (2000) Role of hepatic lipogenesis in the susceptibility to fatty liver in the goose (Anser anser). Comp Biochem Physiol B 126:81–87
Molette C, Berzaghi P, Zotte AD, Remignon H, Babile R (2001) The use of near-infrared reflectance spectroscopy in the prediction of the chemical composition of goose fatty liver. Poult Sci 80:1625–1629
Malhi H, Bronk SF, Werneburg NW, Gores GJ (2006) Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem 281:12093–12101
Donato MT, Lahoz A, Jimenez N, Perez G, Serralta A, Mir J, Castell JV, Gomez-Lechon MJ (2006) Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab Dispos 34:1556–1562
Miller TA, LeBrasseur NK, Cote GM, Trucillo MP, Pimentel DR, Ido Y, Ruderman NB, Sawyer DB (2005) Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes. Biochem Biophys Res Commun 336:309–315
Ricchi M, Odoardi MR, Carulli L, Anzivino C, Ballestri S, Pinetti A, Fantoni LI, Marra F, Bertolotti M, Banni S, Lonardo A, Carulli N, Loria P (2009) Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol 24:830–840
Joshi-Barve S, Barve SS, Amancherla K, Gobejishvili L, Hill D, Cave M, Hote P, McClain CJ (2007) Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology 46:823–830
Fong DG, Nehra V, Lindor KD, Buchman AL (2000) Metabolic and nutritional considerations in nonalcoholic fatty liver. Hepatology 32:3–10
Fournier E, Peresson R, Guy G, Hermier D (1997) Relationships between storage and secretion of hepatic lipids in two breeds of geese with different susceptibility to liver steatosis. Poult Sci 76:599–607
Bradbury MW (2006) Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: possible role in steatosis. Am J Physiol Gastrointest Liver Physiol 290:G194–G198
Hermier D, Forgez P, Laplaud PM, Chapman MJ (1988) Density distribution and physicochemical properties of plasma lipoproteins and apolipoproteins in the goose, Anser anser, a potential model of liver steatosis. J Lipid Res 29:893–907
Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol 13:29–83
Natali F, Siculella L, Salvati S, Gnoni GV (2007) Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells. J Lipid Res 48:1966–1975
Gomez-Lechon MJ, Ponsoda X, O’Connor E, Donato T, Castell JV, Jover R (2003) Diclofenac induces apoptosis in hepatocytes by alteration of mitochondrial function and generation of ROS. Biochem Pharmacol 66:2155–2167
Mori M, Itabe H, Higashi Y, Fujimoto Y, Shiomi M, Yoshizumi M, Ouchi Y, Takano T (2001) Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum. J Lipid Res 42:1771–1781
Pan Z, Wang J, Kang B, Lu L, Han C, Tang H, Li L, Xu F, Zhou Z, Lv J (2010) Screening and identification of differentially expressed genes in goose hepatocytes exposed to free fatty acid. J Cell Biochem 111:1482–1492
Pan Z, Wang J, Han C, Zhai N, Lv J, Zhou Z, Tang H, Xiang S, Li L (2010) Identification of differentially expressed genes between hepatocytes of Landes geese (Anser anser) and Sichuan white geese (Anser cygnoides). Mol Biol Rep 37:4059–4066
Fossati P, Prencipe L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28:2077–2080
Gomez-Lechon MJ, Donato MT, Martinez-Romero A, Jimenez N, Castell JV, O’Connor JE (2007) A human hepatocellular in vitro model to investigate steatosis. Chem Biol Interact 165:106–116
Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 100:3077–3082
Lee JY, Cho HK, Kwon YH (2010) Palmitate induces insulin resistance without significant intracellular triglyceride accumulation in HepG2 cells. Metabolism 59:927–934
Pilo B, George JC (1983) Diurnal and seasonal variation in liver glycogen and fat in relation to metabolic status of liver and M. pectoralis in the migratory starling, Sturnus roseus, wintering in India. Comp Biochem Physiol A 74:601–604
Shi Y, Cheng D (2009) Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism. Am J Physiol Endocrinol Metab 297:E10–E18
Liu Y, Millar JS, Cromley DA, Graham M, Crooke R, Billheimer JT, Rader DJ (2008) Knockdown of acyl-CoA:diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice. Biochim Biophys Acta 1781:97–104
Villanueva CJ, Monetti M, Shih M, Zhou P, Watkins SM, Bhanot S, Farese RV Jr (2009) Specific role for acyl CoA:Diacylglycerol acyltransferase 1 (Dgat1) in hepatic steatosis due to exogenous fatty acids. Hepatology 50:434–442
Nagasawa T, Inada Y, Nakano S, Tamura T, Takahashi T, Maruyama K, Yamazaki Y, Kuroda J, Shibata N (2006) Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARδ agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet. Eur J Pharmacol 536:182–191
Jambor de Sousa UL, Koss MD, Fillies M, Gahl A, Scheeder MR, Cardoso MC, Leonhardt H, Geary N, Langhans W, Leonhardt M (2005) CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells. Biochem Biophys Res Commun 338:757–761
Wan J, Jiang L, Lu Q, Ke L, Li X, Tong N (2010) Activation of PPARδ up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic β-cells. Biochem Biophys Res Commun 391:1567–1572
Henique C, Mansouri A, Fumey G, Lenoir V, Girard J, Bouillaud F, Prip-Buus C, Cohen I (2010) Increased mitochondrial fatty acid oxidation is sufficient to protect skeletal muscle cells from palmitate-induced apoptosis. J Biol Chem 285:36818–36827
Munoz MC, Argentino DP, Dominici FP, Turyn D, Toblli JE (2006) Irbesartan restores the in vivo insulin signaling pathway leading to Akt activation in obese Zucker rats. J Hypertens 24:1607–1617
Kamagate A, Qu S, Perdomo G, Su D, Kim DH, Slusher S, Meseck M, Dong HH (2008) FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. J Clin Invest 118:2347–2364
Uyeda K, Yamashita H, Kawaguchi T (2002) Carbohydrate responsive element-binding protein (ChREBP): a key regulator of glucose metabolism and fat storage. Biochem Pharmacol 63:2075–2080
Acknowledgment
The study was supported by the earmarked fund for Modern Agro-industry Technology Research System, no: NYCYTX-45-05.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pan, Z., Wang, J., Tang, H. et al. Effects of palmitic acid on lipid metabolism homeostasis and apoptosis in goose primary hepatocytes. Mol Cell Biochem 350, 39–46 (2011). https://doi.org/10.1007/s11010-010-0680-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-010-0680-6