In light of the recent pandemic, people across the globe are increasingly becoming aware of the importance of consistent high-quality nutrition and every day exercise. Multiple studies have already demonstrated the positive and negative effects of assorted dietary constituents on human health. More specifically, prior studies conducted on certain forms of transgenic mice have shown that fat-rich diets comprising trans-fatty acid (TFA), saturated fatty acid (SFA), and cholesterol cause non-alcoholic fatty liver disease, which can then promote inflammation and tumor formation within the liver. Nonetheless, the precise effects of dietary fat compositions have remained unknown to date.

Researchers led by Professor Naoki Tanaka from the Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Japan, have recently endeavored to fine-tune previous findings and fill on this gap in knowledge. Using experiments involving transgenic mice, they’ve successfully shown that dietary saturated/trans fats, but not cholesterol, can trigger hepatic angiogenesis and lymphangiogenesis, resulting in the promotion of hepatic tumors. Angiogenesis (the formation of latest blood vessels) and lymphangiogenesis (formation of latest lymphatic vessels), i.e., neovasculogenesis, are key determinants for the survival, proliferation, and metastasis of cancer cells.

In response to Prof. Tanaka, “Dietary TFA, SFA, and cholesterol are present in quite a lot of food sources. For example, cholesterol is abundant in animal-derived foods like eggs, cheese, shellfish, meats, sardines, and full-fat yogurt. Whereas SFA is primarily present in animal and plant products resembling beef, dairy items, palm oil, and coconut oil, TFA naturally occurs in dairy products and animal meat in relatively smaller amounts. Certain products, resembling partially hydrogenated vegetable oils, contain relatively larger amounts of TFA.”

To check the association between dietary fat composition and liver neovasculogenesis, the researchers fed hepatitis C virus core gene transgenic (HCVcpTg) mice with a control weight loss plan or with TFA-/SFA-/cholesterol-rich diets containing the identical variety of calories. The cholesterol weight loss plan comprised ingredients with 1.5% cholesterol, the SFAs were derived from hydrogenated coconut oil, and the TFA weight loss plan consisted of shortening. The researchers then monitored the degree of hepatic angiogenesis and lymphangiogenesis and growth factor expression using quite a lot of techniques including quantitative mRNA measurement, immunoblot evaluation, and immunohistochemistry. They reported their findings in an article that was made available online on 16 September 2022 and subsequently published in Liver Cancer.

Says Prof. Tanaka, “Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators like CD31 and TEK receptor tyrosine kinase, along with lymphatic vessel endothelial hyaluronan receptor 1. We also detected elevated levels of vascular endothelial growth factor C and fibroblast growth factor receptors 2 and three, in addition to c-Jun N-terminal kinase and hypoxia-inducible factor 1α within the mice livers.” Incidentally, vascular endothelial growth factor C (VEGF-C), fibroblast growth factor (FGF) receptors 2 and three, c-Jun N-terminal kinase (JNK), and hypoxia-inducible factor (HIF) 1α are vital biomolecules involved in cell communication and growth signaling. JNK-HIF1α-VEGF-C axis and FGFs are thus powerful drivers of hepatic neovasculogenesis.

What does this information translate to? Increased formation of latest blood and lymphatic vessels within the liver.

But this will likely not necessarily be bad news. In response to Prof. Tanaka , “We demonstrated for the primary time that hepatic angiogenesis and lymphangiogenesis were enhanced by saturated-fat- or trans-fat-rich diets, but not cholesterol-rich diets, mainly through the JNK-HIF1α-VEGF-C axis. These processes are crucial targets for treating hepatocellular carcinoma.”

He further adds: “Agents inhibiting hepatic angiogenesis are widely used for treating hepatocellular carcinoma. Nonetheless, I also recommend avoiding fatty-acid-rich diets especially if someone is at a high risk of developing liver cancer or undergoing treatment for liver cancer.”

Besides monitoring our food intake, the researchers also recommend developing newer methods of food production that may significantly decrease the generation of trans-fatty acids in foods. This, based on their observations on this study, is consistent with the World Health Organization’s call for global elimination of industrially-generated trans-fatty acids from our food supplies by 2023 under the “REPLACE” motion package.

Saying no to French fries is probably not that easy, but within the interest of our hepatic health, we could need to, because of these insightful findings by the researchers of Shinshu University.

Source:

Journal reference:

Diao, P., et al. (2022) Dietary Fat Composition Affects Hepatic Angiogenesis and Lymphangiogenesis in Hepatitis C Virus Core Gene Transgenic Mice. Liver Cancer. doi.org/10.1159/000525546.