Choline intake in a large cohort of patients with nonalcoholic fatty liver disease

Guerrerio, Anthony L.; Colvin, Ryan; Schwartz, Amy K.; Molleston, Jean P.; Murray, Karen F.; Diehl, Anna Mae; Mohan, Parvathi; Schwimmer, Jeffrey B.; Lavine, Joel E.; Torbenson, Michael; Scheimann, Ann O.

doi:10.3945/ajcn.111.020156

Cited by 111 publications

(87 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Experiments in rodents have revealed molecular underpinnings of liver fat accumulation using methionine and choline deficient (MCD) diets [30,41], and diminished choline intake has also been associated with a more aggressive NAFLD course in humans [42]. The ability of experimental MCD diets to trigger steatosis and liver injury is facilitated by abundant mono- or disaccharides in the diet, because replacing these simple carbohydrates with starch markedly ameliorates the adverse histopathological effects of the MCD diet, a portion of which is hypothesized to occur through increased de novo lipogenesis [31,43].…”

Section: Discussionmentioning

confidence: 99%

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

et al. 2013

View full text Add to dashboard Cite

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet – weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction – were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Studies simulating methyl-deficient diets have reported disorders in protein synthesis in the liver and fatty liver as well as muscle disturbances [24,25,26]. Betaine [27,28,29,30], choline, or folate [31] were able to reverse alcohol-related or non-alcohol related liver disturbances, probably via epigenetic regulation [32] or lipid-related mechanisms.…”

Section: Metabolic Burden Of a Methyl-deficient Dietmentioning

confidence: 99%

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

2013

View full text Add to dashboard Cite

Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver. The link between choline, betaine, and energy metabolism in humans indicates novel functions for these nutrients. This function appears to goes beyond the role of the nutrients in gene methylation and epigenetic control. Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders. Changes in plasma concentrations of total homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl group deficiency or nutrient supplementations. Folic acid supplementation spares betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy, particularly in case of folate deficiency, methionine load, or alcohol consumption. Betaine supplementation has a lowering effect on post-methionine load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available.

show abstract

“…This is supported by data in humans showing that dietary choline deprivation leads to the development of fatty liver differentially depending on sex and genetic variations in 1‐carbon genes (6–8). A recent publication showed that, in biopsy‐characterized postmenopausal women, low choline intake was associated with worse fibrosis (27), highlighting choline as an important nutrient in NAFLD progression. Our study provides novel insights into the contributions of choline‐related SNPs to steatosis severity.…”

Section: Discussionmentioning

confidence: 99%

Genetic signatures in choline and 1‐carbon metabolism are associated with the severity of hepatic steatosis

et al. 2013

View full text Add to dashboard Cite

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.

show abstract

Choline intake in a large cohort of patients with nonalcoholic fatty liver disease

Cited by 111 publications

References 63 publications

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

Genetic signatures in choline and 1‐carbon metabolism are associated with the severity of hepatic steatosis

Contact Info

Product

Resources

About