Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans

Fredrik Rosqvist; David Iggman; Joel Kullberg; Jonathan Cedernaes; Hans-Erik Johansson; Anders Larsson; Lars Johansson; Håkan Ahlström; Peter Arner; Ingrid Dahlman; and Ulf Risérus


Diabetes. 2014;63(7):2356-2368. 

In This Article

Abstract and Introduction


Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body composition during overfeeding saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs). LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs (palm oil) or n-6 PUFAs (sunflower oil) for 7 weeks. Liver fat, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), total adipose tissue, pancreatic fat, and lean tissue were assessed by magnetic resonance imaging. Transcriptomics were performed in SAT. Both groups gained similar weight. SFAs, however, markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs. Conversely, PUFAs caused a nearly threefold larger increase in lean tissue than SFAs. Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs. Genes involved in regulating energy dissipation, insulin resistance, body composition, and fat-cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFAs in SAT. In conclusion, overeating SFAs promotes hepatic and visceral fat storage, whereas excess energy from PUFAs may instead promote lean tissue in healthy humans.


Fat accumulation in the liver, pancreas, and abdomen may have long-term, adverse metabolic consequences.[1–3] Although obesity is a major health concern, abdominal obesity is of greater clinical relevance. Accumulation of liver fat, including nonalcoholic fatty liver disease (NAFLD), is present in ~25% of adults in Western countries and has been proposed as a causative factor in the development of cardiometabolic disorders and type 2 diabetes.[4–8] In obesity, the prevalence of NAFLD is extremely high and may reach 75%.[9] Thus, liver fat may be a key target in the prevention and treatment of metabolic diseases. Why certain individuals deposit liver fat to a larger extent than others during weight gain is unknown. High-fat diets have been shown to increase liver fat in both humans and rodents when compared with low-fat diets.[10–12] Cross-sectional data suggest that dietary fat composition could play a key role in liver fat accumulation with polyunsaturated fatty acids (PUFAs) inversely[13] and saturated fatty acids (SFAs) directly associated with liver fat and liver fat markers.[14,15] In addition, animals fed high-fat diets with PUFAs reduced body and liver fat accumulation compared with SFA diets.[16–21] In the recent HEPFAT trial, we showed that an isocaloric diet rich in PUFAs given for 10 weeks reduced liver fat content and tended to reduce insulin resistance compared with a diet rich in SFAs in individuals with abdominal obesity and type 2 diabetes.[22]

Overweight and obesity are mainly results of long-term energy excess. To prevent early excessive adiposity and its metabolic consequences, it is necessary to investigate dietary factors that could initially influence body fat accumulation and ectopic fat storage. We hypothesized that liver fat accumulation during moderate weight gain could be counteracted if the excess energy originates mainly from PUFAs rather than from SFAs. The aim was to investigate the effects of excess intake of the major n-6 PUFAs in the diet, linoleic acid, or the major SFAs in the diet, palmitic acid, on liver fat accumulation, body composition, and adipose tissue gene expression in healthy, normal-weight individuals.