Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

doi:10.1016/j.jcmgh.2018.07.004

Review

. 2018 Aug 23;6(4):451-462.

doi: 10.1016/j.jcmgh.2018.07.004. eCollection 2018.

Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

Octavia Pickett-Blakely¹, Kimberly Young¹, Rotonya M Carr¹

Affiliations

PMID: 30294653
PMCID: PMC6170520
DOI: 10.1016/j.jcmgh.2018.07.004

Free PMC article

Review

Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

Octavia Pickett-Blakely et al. Cell Mol Gastroenterol Hepatol. 2018.

Free PMC article

. 2018 Aug 23;6(4):451-462.

doi: 10.1016/j.jcmgh.2018.07.004. eCollection 2018.

Authors

Octavia Pickett-Blakely¹, Kimberly Young¹, Rotonya M Carr¹

Affiliation

¹ Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.

PMID: 30294653
PMCID: PMC6170520
DOI: 10.1016/j.jcmgh.2018.07.004

Abstract

Micronutrients include electrolytes, minerals, vitamins, and carotenoids, and are required in microgram or milligram quantities for cellular metabolism. The liver plays an important role in micronutrient metabolism and this metabolism often is altered in chronic liver diseases. Here, we review how the liver contributes to micronutrient metabolism; how impaired micronutrient metabolism may be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a systemic disorder of energy, glucose, and lipid homeostasis; and how insights gained from micronutrient biology have informed NAFLD therapeutics. Finally, we highlight some of the challenges and opportunities that remain with investigating the contribution of micronutrients to NAFLD pathology and suggest strategies to incorporate our understanding into the care of NAFLD patients.

Keywords: ALT, alanine aminotransferase; BMI, body mass index; FXR, farnesoid X receptor; IL, interleukin; Micronutrients; NAFLD; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Obesity; ROS, reactive oxygen species; TGF, transforming growth factor; Vitamins; carotenoids; minerals.

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Figures

**Figure 1**
**Micronutrients and the liver in NAFLD.** Hepatic contribution to metabolism of the micronutrients involved in NAFLD pathogenesis. Vit., vitamin.

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References

1. Carr R.M., Oranu A., Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am. 2016;45:639–652. - PMC - PubMed
1. Speliotes E.K., Yerges-Armstrong L.M., Wu J., Hernaez R., Kim L.J., Palmer C.D., Gudnason V., Eiriksdottir G., Garcia M.E., Launer L.J., Nalls M.A., Clark J.M., Mitchell B.D., Shuldiner A.R., Butler J.L., Tomas M., Hoffmann U., Hwang S.J., Massaro J.M., O'Donnell C.J., Sahani D.V., Salomaa V., Schadt E.E., Schwartz S.M., Siscovick D.S., Voight B.F., Carr J.J., Feitosa M.F., Harris T.B., Fox C.S., Smith A.V., Kao W.H., Hirschhorn J.N., Borecki I.B. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7 e1001324. - PMC - PubMed
1. Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465. - PMC - PubMed
1. Abul-Husn N.S., Cheng X., Li A.H., Xin Y., Schurmann C., Stevis P., Liu Y., Kozlitina J., Stender S., Wood G.C., Stepanchick A.N., Still M.D., McCarthy S., O'Dushlaine C., Packer J.S., Balasubramanian S., Gosalia N., Esopi D., Kim S.Y., Mukherjee S., Lopez A.E., Fuller E.D., Penn J., Chu X., Luo J.Z., Mirshahi U.L., Carey D.J., Still C.D., Feldman M.D., Small A., Damrauer S.M., Rader D.J., Zambrowicz B., Olson W., Murphy A.J., Borecki I.B., Shuldiner A.R., Reid J.G., Overton J.D., Yancopoulos G.D., Hobbs H.H., Cohen J.C., Gottesman O., Teslovich T.M., Baras A., Mirshahi T., Gromada J., Dewey F.E. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–1106. - PMC - PubMed
1. Browning J.D., Szczepaniak L.S., Dobbins R., Nuremberg P., Horton J.D., Cohen J.C., Grundy S.M., Hobbs H.H. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395. - PubMed

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[1] Carr R.M., Oranu A., Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am. 2016;45:639–652. - PMC - PubMed

[2] Carr R.M., Oranu A., Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am. 2016;45:639–652. - PMC - PubMed

[3] Speliotes E.K., Yerges-Armstrong L.M., Wu J., Hernaez R., Kim L.J., Palmer C.D., Gudnason V., Eiriksdottir G., Garcia M.E., Launer L.J., Nalls M.A., Clark J.M., Mitchell B.D., Shuldiner A.R., Butler J.L., Tomas M., Hoffmann U., Hwang S.J., Massaro J.M., O'Donnell C.J., Sahani D.V., Salomaa V., Schadt E.E., Schwartz S.M., Siscovick D.S., Voight B.F., Carr J.J., Feitosa M.F., Harris T.B., Fox C.S., Smith A.V., Kao W.H., Hirschhorn J.N., Borecki I.B. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7 e1001324. - PMC - PubMed

[4] Speliotes E.K., Yerges-Armstrong L.M., Wu J., Hernaez R., Kim L.J., Palmer C.D., Gudnason V., Eiriksdottir G., Garcia M.E., Launer L.J., Nalls M.A., Clark J.M., Mitchell B.D., Shuldiner A.R., Butler J.L., Tomas M., Hoffmann U., Hwang S.J., Massaro J.M., O'Donnell C.J., Sahani D.V., Salomaa V., Schadt E.E., Schwartz S.M., Siscovick D.S., Voight B.F., Carr J.J., Feitosa M.F., Harris T.B., Fox C.S., Smith A.V., Kao W.H., Hirschhorn J.N., Borecki I.B. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7 e1001324. - PMC - PubMed

[5] Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465. - PMC - PubMed

[6] Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465. - PMC - PubMed

[7] Abul-Husn N.S., Cheng X., Li A.H., Xin Y., Schurmann C., Stevis P., Liu Y., Kozlitina J., Stender S., Wood G.C., Stepanchick A.N., Still M.D., McCarthy S., O'Dushlaine C., Packer J.S., Balasubramanian S., Gosalia N., Esopi D., Kim S.Y., Mukherjee S., Lopez A.E., Fuller E.D., Penn J., Chu X., Luo J.Z., Mirshahi U.L., Carey D.J., Still C.D., Feldman M.D., Small A., Damrauer S.M., Rader D.J., Zambrowicz B., Olson W., Murphy A.J., Borecki I.B., Shuldiner A.R., Reid J.G., Overton J.D., Yancopoulos G.D., Hobbs H.H., Cohen J.C., Gottesman O., Teslovich T.M., Baras A., Mirshahi T., Gromada J., Dewey F.E. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–1106. - PMC - PubMed

[8] Abul-Husn N.S., Cheng X., Li A.H., Xin Y., Schurmann C., Stevis P., Liu Y., Kozlitina J., Stender S., Wood G.C., Stepanchick A.N., Still M.D., McCarthy S., O'Dushlaine C., Packer J.S., Balasubramanian S., Gosalia N., Esopi D., Kim S.Y., Mukherjee S., Lopez A.E., Fuller E.D., Penn J., Chu X., Luo J.Z., Mirshahi U.L., Carey D.J., Still C.D., Feldman M.D., Small A., Damrauer S.M., Rader D.J., Zambrowicz B., Olson W., Murphy A.J., Borecki I.B., Shuldiner A.R., Reid J.G., Overton J.D., Yancopoulos G.D., Hobbs H.H., Cohen J.C., Gottesman O., Teslovich T.M., Baras A., Mirshahi T., Gromada J., Dewey F.E. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–1106. - PMC - PubMed

[9] Browning J.D., Szczepaniak L.S., Dobbins R., Nuremberg P., Horton J.D., Cohen J.C., Grundy S.M., Hobbs H.H. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395. - PubMed

[10] Browning J.D., Szczepaniak L.S., Dobbins R., Nuremberg P., Horton J.D., Cohen J.C., Grundy S.M., Hobbs H.H. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395. - PubMed

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Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

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Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

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