Non‐alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin‐based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole‐body metabolic pathologies in many areas of the world.
The effect of choline metabolite betaine on alleviation of metabolic syndrome phenotype was investigated in CTP: phosphoethanolamine cytidylyltransferase knockout mice (ETKO). Adult ETKO gradually develop liver steatosis, obesity, hyperlipidemia, and insulin resistance even on a chow diet. Obese ETKO and lean 34‐week old wild‐type littermates (WT) were subjected to normal chow diet and supplemented with or without 1% betaine in drinking water for 8 weeks. The food and water intake along with total body weight were continuously monitored and the plasma and tissues lipid content, adipocyte size and liver steatosis were investigated at the end of the treatment. In 8 weeks, untreated ETKO and WT similarly gained 9.7%–10.4% of their initial body weight. Betaine treated ETKO however lost 4.2% of total body weight and there was no betaine effect on WT littermate weight. Treated ETKO plasma triglycerides (TAG) were reduced 40.9% and liver diacylglycerol (DAG) and TAG were reduced by 50% and 37.4% respectively. Significant reductions in adipocyte size and lipid droplet content in treated ETKO livers were histologically observed. The ETKO genes involved in liver lipogenesis including sterol regulatory element binding protein‐1 (SREBP‐1c), fatty acid synthase (FAS), stearoyl‐CoA desaturase (SCD‐1), diglyceride acyltransferase‐1 (DGAT‐1) and diglyceride acyltransferase‐2 (DGAT‐2), had significantly reduced levels of expression after betaine treatments. Mitochondrial genes for fatty acid oxidation such as peroxisome proliferator‐activated receptor alpha (PPARα) and peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), were on the other hand up‐regulated in comparison to betaine untreated ETKO. The data demonstrates a positive effect of betaine in improving negative effects of obesity and on overall lipid metabolism and mitochondrial function.Grant Funding Source : Ontario Ministry of Agriculture, Food, and Rural affairs
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