Dairy consumption and hepatocellular carcinoma risk

Abstract

This review provides epidemiological and translational evidence for milk and dairy intake as critical risk factors in the pathogenesis of hepatocellular carcinoma (HCC). Large epidemiological studies in the United States and Europe identified total dairy, milk and butter intake with the exception of yogurt as independent risk factors of HCC. Enhanced activity of mechanistic target of rapamycin complex 1 (mTORC1) is a hallmark of HCC promoted by hepatitis B virus (HBV) and hepatitis C virus (HCV). mTORC1 is also activated by milk protein-induced synthesis of hepatic insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (BCAAs), abundant constituents of milk proteins. Over the last decades, annual milk protein-derived BCAA intake increased 3 to 5 times in Western countries. In synergy with HBV-and HCV-induced secretion of hepatocyte-derived exosomes enriched in microRNA-21 (miR-21) and miR-155, exosomes of pasteurized milk as well deliver these oncogenic miRs to the human liver. Thus, milk exosomes operate in a comparable fashion to HBV-or HCV-induced exosomes. Milk-derived miRs synergistically enhance IGF-1-AKT-mTORC1 signaling and promote mTORC1-dependent translation, a meaningful mechanism during the postnatal growth phase, but a long-term adverse effect promoting the development of HCC. Both, dietary BCAA abundance combined with oncogenic milk exosome exposure persistently overstimulate hepatic mTORC1. Chronic alcohol consumption as well as type 2 diabetes mellitus (T2DM), two HCC-related conditions, increase BCAA plasma levels. In HCC, mTORC1 is further hyperactivated due to RAB1 mutations as well as impaired hepatic BCAA catabolism, a metabolic hallmark of T2DM. The potential HCC-preventive effect of yogurt may be caused by lactobacilli-mediated degradation of BCAAs, inhibition of branched-chain α-ketoacid dehydrogenase kinase via production of intestinal medium-chain fatty acids as well as degradation of milk exosomes including their oncogenic miRs. A restriction of total animal protein intake realized by a vegetable-based diet is recommended for the prevention of HCC.

The Immune System through the Lens of Alcohol Intake and Gut Microbiota

“…Specifically, chronic alcohol consumption could reduce the SCFAs count through the reduction in some Firmicutes genera, such as Faecalibacterium and Ruminococcaceae , on which the production of SCFAs depends [ 75 , 76 ]. Furthermore, it has been described that alcohol consumption would also have effects on other microbiota derived metabolites, leading to increases in branched-chain amino acids [ 77 ] and peptidoglycans [ 78 ]. However, studies showing the effect of alcohol on these microbiota derived metabolites are scarce.…”

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

“…Importantly, DLBCL cells take up exosomes and their RNAs [ 274 ]. This observation highlights the importance of EVs and exosomes promoting aberrant biological programming of recipient cells, including pre-metastatic niche formation and tumor progression [ 274 , 275 ], also demonstrated in other malignancies such as B-cell chronic lymphocytic leukemia [ 276 ], melanoma [ 277 , 278 ], pancreatic cancer [ 279 ], hepatocellular carcinoma [ 280 , 281 ], breast cancer [ 282 , 283 ], and prostate cancer [ 284 , 285 ]. Of note, CLL-derived microvesicles (MV) can activate the AKT/mTORC1/p70S6K/hypoxia-inducible factor-1α axis in CLL-bone marrow stromal cells (BMSCs) with the production of vascular endothelial growth factor, a survival factor for CLL B-cells.…”

Age-Related Dietary Habits and Blood Biochemical Parameters in Patients with and without Steatosis—MICOL Cohort

“…Furthermore, the literature declares a neutral role of wheat consumption in the development of steatosis without investigating the age of the subjects [ 39 ], while with regard to the consumption of dairy products, there are conflicting results. Indeed, Melkin et al [ 40 ] claim a negative role for the development of steatosis, while Lee et al [ 41 ] attribute to dairy products a protective role associated with the risk of incident steatosis in men and women aged >50 years. Similarly, processed meat in adults and seafood/shellfish in elderly patients have been confirmed to be associated with liver disease [ 42 ].…”