The Effect of Oleic and Palmitic Acid on Induction of Steatosis and Cytotoxicity on Rat Hepatocytes in Primary Culture

Abstract

In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5-1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production.OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone.In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone.

p62/SQSTM1—Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer

“…NRF2 suppresses expression of key enzymes involved in fatty acid synthesis . p62‐induced NRF2 activation protects cells from lipotoxicity induced by palmitic acid , which is the most abundant fatty acid in human serum and an inducer of pro‐inflammatory cytokines, including TNF, IL‐6 and IL‐8, and ROS production . Together with the results described above, it appears that the p62–Keap1–NRF2 axis slows down NASH development (Fig.…”

Influence of oleic acid in different solvent media on BRL 3A cell growth and viability

“…The BRL3A rat liver cell line was purchased from Stem Cell Bank, Chinese Academy of Sciences (Shanghai, China) and cultured in DMEM (GIBCO, Life Technologies, USA) containing 10% FBS (GIBCO, Life Technologies) with 1% Penicillin-Streptomycin Solution (Solarbio Life Sciences, Beijing, China) in a humidified incubator at 37ºC with 5% CO 2 . Stock solutions of 158.5 µl OA were prepared in 10 ml of 0.1 mM KOH , 0.1 mM PBS, alcohol (absolute ethyl ethanol; Lagrutta et al, 2017, Liao et al, 2014, BSA (0.4%, 0.8%, 1.2%) (Moravcova et al, 2015, Seo et al, 2014 and DMSO (0.1%, 0.4%, 0.8%) (Rogue et al, 2014, Zhang et al, 2004, respectively, and diluted in DMEM culture medium to a final concentration of OA at 1.2 mM. About 5×10 4 BRL 3A cells per well were seeded on the six-well culture plates and treated with different solvents and OA in different solvents.…”

Liver‐on‐a‐Chip Models of Fatty Liver Disease

“…(21) OA, PA, and their mixtures led to increased accumulation of intracellular triacylglycerols (TAGs), but PA led to a dose-dependent cytotoxic effect associated with an increase in reactive oxygen species (ROS) and decreased albumin production. (21) With this in mind, NAFLD-on-a-chip was created with a central chamber containing HepG2 cells surrounded by closely spaced, parallel microchannels to simulate endothelial cells. To minimize shear stress, media flowed through a separate chamber connected to the central chamber by microchannels.…”