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Cited by 211Liver Disease Diagnosis and TreatmentDiet, Metabolism, and DiseaseAlcohol Consumption and Health Effects

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans

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Sevastianova, Ksenia, Santos, Alexandre, Kotronen, Anna, Hakkarainen, Antti, Makkonen, Janne, Silander, Kaisa, Peltonen, Markku, Romeo, Stefano, Lundbom, Jesper, Lundbom, Nina, Olkkonen, Vesa M, Gylling, Helena, Fielding, Barbara A, Rissanen, Aila, Yki-Järvinen, Hannele·2012·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.112.038695
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Abstract

Background Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD).Objective We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss.Design Sixteen subjects [BMI (kg/m²): 30.6 ± 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL.Results Carbohydrate overfeeding increased weight (±SEM) by 2% (1.8 ± 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 ± 1.9% to 11.7 ± 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148IIbut not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 ± 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 ± 1.9% to 8.8 ± 1.8%; P < 0.05).Conclusions Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780.

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Crossref · 10.3945/ajcn.112.038695

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Metadata

Authors
Sevastianova, K., Santos, A., Kotronen, A., Hakkarainen, A., Makkonen, J., Silander, K., Peltonen, M., Romeo, S., Lundbom, J., Lundbom, N., Olkkonen, V. M., Gylling, H., Fielding, B. A., Rissanen, A., & Yki-Järvinen, H.
Affiliations
  • Minerva Foundation (FI)
  • Institute for Molecular Medicine Finland (FI)
Corresponding author
Sevastianova, Ksenia
ORCID
Venue
The American Journal of Clinical Nutrition
Publisher
Elsevier BV
Published
2012-10
Volume
96
Issue
4
Pages
727-734
ISSN
0002-9165 (ISSN-L)
DOI
10.3945/ajcn.112.038695
OpenAlex
W2144702146
Cited by
211
References
51
Citations by year
2026: 2 · 2025: 11 · 2024: 9 · 2023: 17 · 2022: 10 · 2021: 13 · 2020: 21 · 2019: 20 · 2018: 9 · 2017: 17 · 2016: 20 · 2015: 24 · 2014: 9 · 2013: 25 · 2012: 4
FWCI
14.85
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Clinical Nutrition (publishedVersion)
  • PubMed (publishedVersion)
  • Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
non-alcoholic fatty liver disease, liver fat, monosaccharides, de novo lipogenesis, weight loss, hypocaloric diet, hypercaloric diet, PNPLA3, VLDL triglycerides, overweight, serum triglycerides
MeSH terms
Acyltransferases, Adult, Diet, Reducing, Dietary Carbohydrates, Fatty Liver, Female, Humans, Lipase, Lipoproteins, VLDL, Liver, Male, Membrane Proteins, Triglycerides, Hypertriglyceridemia, Weight Gain, Weight Loss, Body Mass Index, Dietary Sucrose, Polymorphism, Single Nucleotide, Lipogenesis, Overweight, Lipid Metabolism, Phospholipases A2, Calcium-Independent, Genetic Association Studies, Non-alcoholic Fatty Liver Disease

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