title: Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans.
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.
  
  
  METHODS
  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.
authors.affiliation: Minerva Foundation Institute for Medical Research, Helsinki, Finland. ksenia.sevastianova@helsinki.fi
authors.forename: Ksenia
authors.initials: K
authors.lastname: Sevastianova
authors.forename: Alexandre
authors.initials: A
authors.lastname: Santos
authors.forename: Anna
authors.initials: A
authors.lastname: Kotronen
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Janne
authors.initials: J
authors.lastname: Makkonen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Markku
authors.initials: M
authors.lastname: Peltonen
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundbom
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Olkkonen
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fielding
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000328:Adult; D015992:Body Mass Index; D004038:Diet, Reducing; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D050155:Lipogenesis; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D050177:Overweight / Q000097:blood / Q000178:diet therapy / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain; D015431:Weight Loss; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D004040:Dietary Carbohydrates; D019422:Dietary Sucrose; D008049:Lipase; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent