(16-10-12) Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans

1,2,3
1. Ksenia Sevastianova,
2. Alexandre Santos,
3. Anna Kotronen,
4. Antti Hakkarainen,
5. Janne Makkonen,
6. Kaisa Silander,
7. Markku Peltonen,
8. Stefano Romeo,
9. Jesper Lundbom,
10. Nina Lundbom,
11. Vesa M Olkkonen,
12. Helena Gylling,
13. Barbara A Fielding,
14. Aila Rissanen, and
15. Hannele Yki-J?rvinen
+Author Affiliations
1. 1From the Minerva Foundation Institute for Medical Research, Helsinki, Finland (K Sevastianova, AS, AK, JM, VMO, and HY-J); the Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland (K Sevastianova, AS, AK, JM, HG, and HY-J); the National Institute for Health and Welfare, Helsinki, Finland (AK, K Silander, and MP); the Department of Radiology, University of Helsinki and HUS Radiology (Helsinki Medical Imaging Center), Helsinki, Finland (AH, JL, and NL); the Institute of Molecular Medicine Finland, University of Helsinki, Helsinki, Finland (K Silander); the Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy (SR); the Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden (SR); the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, and Diabetes and Metabolic Medicine, Institute of Biosciences and Medicine, University of Surrey, Surrey, United Kingdom (BAF); and the Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland (AR)
+Author Notes
? ↵2 Supported by research grants from the Academy of Finland, the Sigrid Juselius Foundation, the Liv och H?lsa Foundation, and the Novo Nordisk Foundation. This work is part of the project ?Hepatic and adipose tissue functions in the metabolic syndrome? (www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (contract LSHM-CT-2005-018734). SR holds a UK Wellcome Trust Starter Grant for Clinical Lecturers (October 2009).
? ↵3 Address correspondence to K Sevastianova, Department of Medicine, University of Helsinki, Biomedicum Helsinki 1, Room C425B, Haartmaninkatu 8, FI-00290 Helsinki, Finland. E-mail: [email protected].
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.

Source: This trial was registered atwww.hus.fi as 235780.
Am J Clin Nutr October 2012vol. 96 no. 4 727-734

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