Differential Lipid Accumulation on HepG2 Cells Triggered by Palmitic and Linoleic Fatty Acids Exposure

Abstract

Lipid metabolism pathways such as β-oxidation, lipolysis and, lipogenesis, are mainly associated with normal liver function. However, steatosis is a growing pathology caused by the accumulation of lipids in hepatic cells due to increased lipogenesis, dysregulated lipid metabolism, and/or reduced lipolysis. Accordingly, this investigation hypothesizes a selective in vitro accumulation of palmitic and linoleic fatty acids on hepatocytes. After assessing the metabolic inhibition, apoptotic effect, and reactive oxygen species (ROS) generation by linoleic (LA) and palmitic (PA) fatty acids, HepG2 cells were exposed to different ratios of LA and PA to study the lipid accumulation using the lipophilic dye Oil Red O. Lipidomic studies were also carried out after lipid isolation. Results revealed that LA was highly accumulated and induced ROS production when compared to PA. Lipid profile modifications were observed after LA:PA 1:1 (v/v) exposure, which led to a four-fold increase in triglycerides (TGs) (mainly in linoleic acid-containing species), as well as a increase in cholesterol and polyunsaturated fatty acids (PUFA) content when compared to the control cells. The present work highlights the importance of balancing both PA and LA fatty acids concentrations in HepG2 cells to maintain normal levels of free fatty acids (FFAs), cholesterol, and TGs and to minimize some of the observed in vitro effects (i.e., apoptosis, ROS generation and lipid accumulation) caused by these fatty acids.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization

“…This work provides additional information for the future use of more sustainable and natural sources of bioactive compounds to replace those currently in use for metabolic syndrome prevention, such as synthetic drugs, which have been shown to exert harmful Similarly, the biocompatibility assay in Hep G2 cells aimed to detect the safe and sublethal concentration of the sugarcane byproduct extract. Since the build-up of lipids in hepatocytes is a pathologic characteristic, it is crucial to investigate how the extract affects these cell types [57]. Again, a concentration under 1.25 mg/mL was considered non-cytotoxic after the 24 h treatment (Figure 9B).…”

“…Similarly, the biocompatibility assay in Hep G2 cells aimed to detect the safe and sublethal concentration of the sugarcane byproduct extract. Since the build-up of lipids in hepatocytes is a pathologic characteristic, it is crucial to investigate how the extract affects these cell types [57]. Again, a concentration under 1.25 mg/mL was considered noncytotoxic after the 24 h treatment (Figure 9B).…”

Allergic inflammation triggers dyslipidemia via IgG signalling

“…Plasma lipid extracts were pooled according to their group, dissolved in IPA/ACN (9:1, v/v) at 0.2 mg/mL and analyzed in triplicate on an UHPLC instrument (Elute; Bruker), equipped with an Acquity UPLC BEH C18 (17 µm) pre-column (Waters), an Intensity Solo 2 C18 (100 x 2.1 mm) column (Bruker), and coupled with an UHR–QTOF detector (Impact II; Bruker). The injection method was based on conditions previously reported with some modifications 74 . Thus, mobile phases consisted of ACN/H 2 O (6:4, v/v) (Phase A) and IPA/ACN (9:1, v/v) (Phase B), each one added with 0.1% (v/v) formic acid and 10 mM ammonium formate.…”

The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer

“…Another LA isomer, beta-eleostearic acid (β-ESA, 9E11E13E-18:3), induces apoptosis through oxidative stress, leading to the accumulation of ROS and a decrease in GSH in T24 human bladder cancer cells [128], as well as in gastric carcinoma cells [30]. Moreover, LA induces ROS production on HepG2 Cells [133]. The involvement of ER stress has also been investigated, with studies reporting intracellular calcium (CA 2+ ) accumulation and the expression of unfolded protein response (UPR)associated genes (CHOP, GRP78, and GRP94) in hepatoma H4IIE cell lines [134].…”