Fatty Livers Produced in Albino Rats by Excess Niacin in High Fat Diets

Rikans, Lora Long; Arata, Dorothy; Cederquist, Dena C.

doi:10.1093/jn/85.1.107

Cited by 16 publications

(6 citation statements)

References 15 publications

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“…Supplementing the diet with methyl donors, such as choline or methionine were reported to prevent fatty livers in rats fed an HFD supplemented with either NA 37 or NAM 18 . Additionally, methylation deficiency-induced liver injury is associated with epigenetic gene modification 21 , with promoter hypomethylation often associated with transcriptional permissiveness.…”

Section: Discussionmentioning

confidence: 99%

NNMT activation can contribute to the development of fatty liver disease by modulating the NAD + metabolism

Komatsu

Kanda

Urai

et al. 2018

Sci Rep

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Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide and S-adenosylhomocysteine. Recently, this enzyme has also been reported to modulate hepatic nutrient metabolism, but its role in the liver has not been fully elucidated. We developed transgenic mice overexpressing NNMT to elucidate its role in hepatic nutrient metabolism. When fed a high fat diet containing NAM, a precursor for nicotinamide adenine dinucleotide (NAD)+, these NNMT-overexpressing mice exhibit fatty liver deterioration following increased expression of the genes mediating fatty acid uptake and decreased very low-density lipoprotein secretion. NNMT overactivation decreased the NAD+ content in the liver and also decreased gene activity related to fatty acid oxidation by inhibiting NAD+–dependent deacetylase Sirt3 function. Moreover, the transgenic mice showed liver fibrosis, with the induction of inflammatory and fibrosis genes. Induced NNMT expression decreased the tissue methylation capacity, thereby reducing methylation of the connective tissue growth factor (CTGF) gene promoter, resulting in increased CTGF expression. These data indicate that NNMT links the NAD+ and methionine metabolic pathways and promotes liver steatosis and fibrosis. Therefore, targeting NNMT may serve as a therapeutic strategy for treating fatty liver and fibrosis.

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Section: Discussionmentioning

confidence: 99%

NNMT activation can contribute to the development of fatty liver disease by modulating the NAD + metabolism

Komatsu

Kanda

Urai

et al. 2018

Sci Rep

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“…46,[49][50][51][52][53][54][55] Our recent studies have shown that there is a strong lag-correlation between the prevalence of obesity and diabetes in the US population and the increased per capita consumption of niacin, which was attributed primarily to the consumption of fortified grains. 34,35 The toxic effects of niacin may involve a variety of mechanisms, including methyl depletion, changes in NAD-dependent reactions and excessive ROS generation.…”

Section: Arsenicmentioning

confidence: 99%

“…Methyl depletion as a consequence of niacin toxicity has been confirmed by the observations that hepatic toxicity can be prevented by choline and betaine supplements. 30,55 It is known that methyl deficiency may limit the formation of very low density lipoprotein and low density lipoprotein in the liver due to decreased phosphatidylcholine synthesis, which may result in a decrease in the levels of plasma very low density lipoprotein and low density lipoprotein, as demonstrated in rats by Mookerjea et al 56 On the other hand, the decreased transport of fat from the liver may lead to an accumulation of fat in the liver, and as a result, fatty liver and steatosis may occur. 57 Moreover, adequate phosphatidylcholine is also required for the formation and clearance of chylomicrons from the intestinal mucosa.…”

Section: Arsenicmentioning

confidence: 99%

“…56 Interestingly, niacin has been found to induce both lipid-lowering effect 52 and adverse hepatic outcomes. 46,52,54,55 Thus, it seems that the lipidlowering effect of niacin may be mediated by methyl depletion, which, although improving cardiovascular outcomes, may increase the risk of adverse hepatic outcomes.…”

Section: Arsenicmentioning

confidence: 99%

“…47,62 Most importantly, long-term highlevel niacin exposure has been observed to induce a methyl-group deficiency state and fatty liver due to an increased need for methylation of niacin in animal studies. 55,63 Based on current evidence, it seems likely that increases in niacin consumption may be correlated to the following phenomena: (1) the prevalence of T2D in the United States has increased in parallel with the increase in per capita consumption of niacin-fortified grains since the implementation of niacin fortification, whereas traditional high intake of non-fortified grain is associated with very low rates of obesity and diabetes; 34 (2) the prevalence of metabolic syndrome-related diseases in niacin-fortified countries is much higher than that of non-fortified developed countries; 34 (3) high consumption of meat, a nicotinamide-rich food, may increase the risk for metabolic syndrome; 64 and (4) consumption of processed meat, in which niacin is used in meat coloring in some non-European countries, can significantly increase the risk of T2D. 65 Catecholamines Catecholamines, primarily norepinephrine and epinephrine that mediate the cardiovascular effect of the sympathetic system, 66 are important endogenous methyl consumers.…”

Section: Arsenicmentioning

confidence: 99%

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Dietary methyl-consuming compounds and metabolic syndrome

Zhou

et al. 2011

Hypertens Res

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The metabolic syndrome, a major risk factor for type 2 diabetes and cardiovascular disease, is a cluster of metabolic abnormalities including obesity, insulin resistance, hypertension and dyslipidemia. Although systemic oxidative stress and aberrant methylation status are known to have important roles in the development of metabolic syndrome, how they occur remains unclear. The metabolism of methyl-consuming compounds generates reactive oxygen species and consumes labile methyl groups; therefore, a chronic increase in the levels of methyl-consuming compounds in the body can induce not only oxidative stress and subsequent tissue injury, but also methyl-group pool depletion and subsequent aberrant methylation status. In the past few decades, the intake amount of methyl-consuming compounds has substantially increased primarily due to pollution, food additives, niacin fortification and high meat consumption. Thus, increased methyl consumers might have a causal role in the development and prevalence of metabolic syndrome and its related diseases. Moreover, factors that decrease the elimination/ metabolism of methyl-consuming compounds and other xenobiotics (for example, sweat gland inactivity and decreased liver function) or increase the generation of endogenous methyl-consuming compounds (for example, mental stress-induced increase in catecholamine release) may accelerate the progression of metabolic syndrome. Based on current nutrition knowledge and the available evidence from epidemiological, ecological, clinical and laboratory studies on metabolic syndrome and its related diseases, this review outlines the relationship between methyl supply-consumption imbalance and metabolic syndrome, and proposes a novel mechanism for the pathogenesis and prevalence of metabolic syndrome and its related diseases.

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The Effects of Combined Treatment with Niacin and Chromium on the Renal Tissues of Hyperlipidemic Rats

et al. 2006

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In this study, 12 months old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I were fed with pellet chow. Group II were fed with pellet chow and treated with 250 microg/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days. Group III were fed a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 2% sunflower oil added to the pellet chow, and given 3%alcoholic water for 60 days. Group IV were fed with the same lipogenic diet for 60 day sand treated by gavage technique to rats at a dose of 250 micro/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days, 15 days after experimental animals were rendered hyperlipidemic. At the 60th day, renal tissue and blood samples were taken from the animals. The sections were examined under light and electron microscopy. The degenerative changes were much more in the hyperlipidemic rats than the control group. The changes in renal tissue were also observed in hyperlipidemic animals given niacin and chromium. In the hyperlipidemic rats, renal glutathione levels decreased and renal lipid peroxidation levels, and serum urea and creatinine levels were increased. But, renal glutathione levels increased and lipid peroxidation levels and serum urea and creatinine levels decreased in hyperlipidemic rats given niacin and chromium. The purpose of this study was to investigate whether a protective effect of a combination of niacin and chromium is present on the renal tissue of hyperlipidemic rats or not. In conclusion, we can say that niacin and chromium do not have a protective effect on the morphology of the renal tissue of hyperlipidemic rats, except a protective effect on their biochemical parameters.

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Fatty Livers Produced in Albino Rats by Excess Niacin in High Fat Diets

Cited by 16 publications

References 15 publications

NNMT activation can contribute to the development of fatty liver disease by modulating the NAD + metabolism

NNMT activation can contribute to the development of fatty liver disease by modulating the NAD + metabolism

Dietary methyl-consuming compounds and metabolic syndrome

The Effects of Combined Treatment with Niacin and Chromium on the Renal Tissues of Hyperlipidemic Rats

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