Advances in Lipotoxicity Research on Hepatocellular Carcinoma
Ming Han Wang, Jun Yuan Han and Quanjun Wang*
Department of Toxicology and Drug Research, Academy of Military Medical Sciences, China
Submission:August 05, 2022; Published: November 01, 2022
*Corresponding author: Quanjun Wang Department of Toxicology and Drug Research, Academy of Military Medical Sciences, China
How to cite this article: Ming H W, Jun Y H, Quanjun W. Advances in Lipotoxicity Research on Hepatocellular Carcinoma. Open Acc J of Toxicol. 2022; 5(3):555664. DOI: 10.19080/OAJT.2022.05.555664.
Abstract
Hepatocellular carcinoma (HCC), a fifth most continual diagnosed cancer, acquires large amounts of free fatty acids (FAs) to promote cell growth. But how the cancer avoids lipotoxicity is unknown. Here, we discussed some lip toxicity research in HCC. Targeting molecules related to lipotoxicity could be a promising therapeutic approach for HCC.
Keywords: Hepatocellular carcinoma; Endoplasmic reticulum; Altered fatty acid; Free fatty acids; Cholesterol ester; Tricarboxylic acid
Abbreviations: HCC: Hepatocellular Carcinoma; ER: Endoplasmic Reticulum; FA: Fatty Acid; FFAs: Free Fatty Acids; CE: Cholesterol Ester; TA: Tricarboxylic Acid
Global Impact of HCC
Hepatocellular Carcinoma (HCC) is the fifth most continual diagnosed cancer and epidemiological studies have authenticated obesity as a crucial risk factor in its development, recently [1-3]. Endoplasmic Reticulum (ER) and oxidative stress, the dysregulation of adipokines, altered gut microbiota and elevated proinflammatory cytokines have been suggested feasible mechanisms underlie obesity-mediated hepatocarcinogenesis, but the process remains dimness [4-8]. Tumour cells undergo typical metabolic changes to fit to their local environment, what is called “metabolic reprogramming” [9]. The most well-studied of these changes is the Warburg effect, in which tumour cells don’t use the normal cellular pathway of mitochondrial oxidative phosphorylation but aerobic glycolysis to exert the energy needed for the synthesis of proteins, nucleic acids and lipids [10]. Altered Fatty Acid (FA) metabolism is another distinction of tumour cells [11].
Lipotoxicity
Lipotoxicity means exposure and accumulation of various lipid species which may cause cellular toxicity or proinflammatory and profibrotic [12]. Relatively small quantities of lipotoxic lipid may exert large negative impact on HCC. While, some others, like omega-3 fatty acids, may decrease lipotoxicity and show a beneficial effect [13]. Potentially lipotoxic molecules include Free Fatty Acids (FFAs) and their derivatives, ceramides [14] diacylglycerol [15] as well ascholesterol [16-18]. FFAs may act in KCs (the resident macrophages of the liver), stellate cells (the cells responsible for most hepatic fibrosis) and hepatocytes [the cells that store most hepatic lipid, including cholesterol and Cholesterol Ester (CE)] and affect insulin signaling, impair membrane function and result in apoptosis [19].
Lipotoxicity Research in HCC
Many studies have reported that lipid metabolism is significantly changed, especially FA synthesis, which is obviously elevated in various types of tumours [20-22]. FAs are synthesized de novo in gross tumour cells, especially in HCC [11,21]. They are essential lipids in cells as they constitute the major structural components of membrane lipids, serve as signalling molecules, an energy source through mitochondria-mediated b-oxidation and Tricarboxylic Acid (TCA) cycle catabolism, storage compounds and incorporation into the cell membrane. However, the enhancive intake of dietary FAs participates with the lipolysis of visceral adipose tissue result in enormous exogenous FA supplies to hepatocytes though the portal vein in obesity [23-26]. This is an extremely feature environment lipid-rich condition for liver cancer, but how the pernicious cells accommodate to it and use it for their recreation is still obscure. Targeting molecules related to lipo toxicity could be a promising therapeutic approach for HCC.
In body packing cases, the clinic is in a broad spectrum and treatment planning is made according to these clinics. In some cases, ileus develops in body packing due to mechanical obstructions and surgical treatment may be required in these cases. In addition, due to the rupture of the packages, toxidrom clinic is developing and appropriate treatment planning is made for these toxidromes. In our case, upon the observation of the packages after imaging and the intense clinical observation of toxidroma, rupture was considered, and appropriate packages were removed from the packages by endoscopic intervention in order to determine the substance and to reduce the retoxicity by preventing the recurrence of package ruptures. Activated charcoal was given to the patient who was found to have body packing and was thought to have possible package rupture. In addition, laxatives were added to the treatment. In the literature, for all body fillers or body packers, osmotic laxatives (lactulose) or polyethylene-glycol (PEG) are recommended in body fillers with activated charcoal [22]. In our case of MAH body packing, we followed up in our emergency critical care area for 5 days after the procedure was completed and the treatment was planned. Since it is ensured that all packages are removed in body packing cases in the literature, follow-up for 2 more days without clinical symptoms is recommended. In addition, it has been reported in the literature that 14% of the cases need a second CT scan to ensure that all packages are removed [23]. In our case, we did not plan a second CT imaging in the critical area follow-up.
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