Cargando…

Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis

Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Vincent L., Wright, Andrew P., Halligan, Brian, Chen, Yanhua, Du, Xiaomeng, Handelman, Samuel K., Long, Michelle T., Kiel, Douglas P., Speliotes, Elizabeth K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671828/
https://www.ncbi.nlm.nih.gov/pubmed/31388628
http://dx.doi.org/10.1002/hep4.1391
_version_ 1783440545343864832
author Chen, Vincent L.
Wright, Andrew P.
Halligan, Brian
Chen, Yanhua
Du, Xiaomeng
Handelman, Samuel K.
Long, Michelle T.
Kiel, Douglas P.
Speliotes, Elizabeth K.
author_facet Chen, Vincent L.
Wright, Andrew P.
Halligan, Brian
Chen, Yanhua
Du, Xiaomeng
Handelman, Samuel K.
Long, Michelle T.
Kiel, Douglas P.
Speliotes, Elizabeth K.
author_sort Chen, Vincent L.
collection PubMed
description Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This study included two cohorts. The first included 2,249 participants from the Framingham Heart Study who underwent a computed tomography scan to evaluate hepatic steatosis, dual‐energy x‐ray absorptiometry testing to assess body composition, and clinical examination. Body composition parameters were normalized to total body weight. A subset of participants underwent genotyping with an Affymetrix 550K single‐nucleotide polymorphism array. The second cohort, Michigan Genomics Initiative, included 19,239 individuals with genotyping on the Illumina HumanCoreExome v.12.1 array and full electronic health record data. Using sex‐stratified multivariable linear regression, greater central body fat associated with increased hepatic steatosis while greater lower extremity body fat associated with decreased hepatic steatosis. Greater appendicular lean mass was associated with decreased hepatic steatosis in men but not in women. A polygenic risk score for lipodystrophy (regional or global loss of adipose tissue) was associated with increased hepatic steatosis, increased liver fibrosis, and decreased lower extremity fat mass. Conclusion: Greater central body fat associated with increased hepatic steatosis, while greater lower extremity body fat and, in men, greater appendicular lean mass were associated with decreased hepatic steatosis. A genetic risk score for lipodystrophy was associated with NAFLD and liver fibrosis. Our results suggest that buffering of excess energy by peripheral fat and muscle may protect against NAFLD and liver fibrosis in the general population.
format Online
Article
Text
id pubmed-6671828
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-66718282019-08-06 Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis Chen, Vincent L. Wright, Andrew P. Halligan, Brian Chen, Yanhua Du, Xiaomeng Handelman, Samuel K. Long, Michelle T. Kiel, Douglas P. Speliotes, Elizabeth K. Hepatol Commun Original Articles Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This study included two cohorts. The first included 2,249 participants from the Framingham Heart Study who underwent a computed tomography scan to evaluate hepatic steatosis, dual‐energy x‐ray absorptiometry testing to assess body composition, and clinical examination. Body composition parameters were normalized to total body weight. A subset of participants underwent genotyping with an Affymetrix 550K single‐nucleotide polymorphism array. The second cohort, Michigan Genomics Initiative, included 19,239 individuals with genotyping on the Illumina HumanCoreExome v.12.1 array and full electronic health record data. Using sex‐stratified multivariable linear regression, greater central body fat associated with increased hepatic steatosis while greater lower extremity body fat associated with decreased hepatic steatosis. Greater appendicular lean mass was associated with decreased hepatic steatosis in men but not in women. A polygenic risk score for lipodystrophy (regional or global loss of adipose tissue) was associated with increased hepatic steatosis, increased liver fibrosis, and decreased lower extremity fat mass. Conclusion: Greater central body fat associated with increased hepatic steatosis, while greater lower extremity body fat and, in men, greater appendicular lean mass were associated with decreased hepatic steatosis. A genetic risk score for lipodystrophy was associated with NAFLD and liver fibrosis. Our results suggest that buffering of excess energy by peripheral fat and muscle may protect against NAFLD and liver fibrosis in the general population. John Wiley and Sons Inc. 2019-06-18 /pmc/articles/PMC6671828/ /pubmed/31388628 http://dx.doi.org/10.1002/hep4.1391 Text en © 2019 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Chen, Vincent L.
Wright, Andrew P.
Halligan, Brian
Chen, Yanhua
Du, Xiaomeng
Handelman, Samuel K.
Long, Michelle T.
Kiel, Douglas P.
Speliotes, Elizabeth K.
Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title_full Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title_fullStr Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title_full_unstemmed Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title_short Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis
title_sort body composition and genetic lipodystrophy risk score associate with nonalcoholic fatty liver disease and liver fibrosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671828/
https://www.ncbi.nlm.nih.gov/pubmed/31388628
http://dx.doi.org/10.1002/hep4.1391
work_keys_str_mv AT chenvincentl bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT wrightandrewp bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT halliganbrian bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT chenyanhua bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT duxiaomeng bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT handelmansamuelk bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT longmichellet bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT kieldouglasp bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis
AT spelioteselizabethk bodycompositionandgeneticlipodystrophyriskscoreassociatewithnonalcoholicfattyliverdiseaseandliverfibrosis