PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity

Alison Mondul, Rosellina M. Mancina, Andrea Merlo, Paola Dongiovanni, Raffaela Rametta, Tiziana Montalcini, Luca Valenti, Demetrius Albanes, Stefano Romeo

Research output: Contribution to journalArticle

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Abstract

Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the a-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and a-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.

Original languageEnglish
Pages (from-to)1687-1691
Number of pages5
JournalJournal of Nutrition
Volume145
Issue number8
DOIs
Publication statusPublished - 2015

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Phospholipases
Vitamin A
Obesity
Alleles
Fasting
Hepatic Stellate Cells
Tocopherols
Carotenoids
Lipase
High Pressure Liquid Chromatography
Genetic Association Studies
Fatty Liver
Non-alcoholic Fatty Liver Disease
Esters
Lipids
Food
Serum
Neoplasms

Keywords

  • NAFLD
  • Obesity
  • PNPLA3
  • RBP4
  • Retinol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity. / Mondul, Alison; Mancina, Rosellina M.; Merlo, Andrea; Dongiovanni, Paola; Rametta, Raffaela; Montalcini, Tiziana; Valenti, Luca; Albanes, Demetrius; Romeo, Stefano.

In: Journal of Nutrition, Vol. 145, No. 8, 2015, p. 1687-1691.

Research output: Contribution to journalArticle

Mondul, Alison ; Mancina, Rosellina M. ; Merlo, Andrea ; Dongiovanni, Paola ; Rametta, Raffaela ; Montalcini, Tiziana ; Valenti, Luca ; Albanes, Demetrius ; Romeo, Stefano. / PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity. In: Journal of Nutrition. 2015 ; Vol. 145, No. 8. pp. 1687-1691.
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abstract = "Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70{\%}] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the a-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and a-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.",
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T1 - PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity

AU - Mondul, Alison

AU - Mancina, Rosellina M.

AU - Merlo, Andrea

AU - Dongiovanni, Paola

AU - Rametta, Raffaela

AU - Montalcini, Tiziana

AU - Valenti, Luca

AU - Albanes, Demetrius

AU - Romeo, Stefano

PY - 2015

Y1 - 2015

N2 - Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the a-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and a-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.

AB - Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the a-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and a-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.

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KW - Obesity

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KW - RBP4

KW - Retinol

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