How reproducible are rat steatosis models using high-fat diets? Reply
Authors: Ki M. Mak, Maria A. Leo
Journal: Journal of Hepatology (2009)

In their Letter to the Editor, Marsman et al. [[1]Marsman HA, Al-Saady RL, Heger M, van Gulik TM. How reproducible are rat steatosis models using high fat diets? J Hepatol 2009. .Google Scholar] raised the question of the reproducibility of Lieber–Decarli (LDC) high-fat diets for the induction of fatty liver in rats [[2]Lieber C.S. Leo M.A. Mak K.M. Xu Y. Cao Q. Ren C. et al.Model of nonalcoholic steatohepatitis.Am J Clin Nutr. 2004; 79: 502-509Crossref PubMed Scopus (361) Google Scholar]. The data presented in the letter revealed a striking difference in gains in body weight between the rats in Marsman's study and those in Lieber's study. The rats (Wistar, sex unknown, N = 5) reported by Marsman et al. had gained 98 g after 21 days of the LCD high-fat diet ad libitum, whereas in Lieber's study, the rats (male Sprague–Dawley, N = 22) had gained 173 g. Thus daily body weight gain in Marsman's study (4.2 g) was only half of that in Lieber'study. (8.2 ± 1.1 g), suggesting an improper methodology in liquid diet feeding, despite, as it was claimed, "following the authors' exact methodology". Furthermore, no caloric intake of the high-fat diet or the control standard diet were indicated in Marsman's letter, while Lieber et al. reported a total caloric intake of 1767 ± 42 kcal in 3 weeks and 86 ± 1.7 kcal daily and a comparable intake of the standard diet. Indeed, gains in body weight of rats (4.2 g/day) in Marsman's feeding protocol were nearly identical to those of rats (4.7 ± 0.1 g, N = 12) fed a restricted high-fat diet (two-thirds of the amount spontaneously consumed by rats fed ad libitum) described by Lieber et al. Since dietary restricted rats developed only modest steatosis compared to panlobular steatosis in rats fed ad libitum, one may wonder whether the lack of fatty liver induction in Marsman's feeding protocol is the result of a lower caloric intake caused by an insufficient consumption of the high-fat diet, reminiscent of the dietary restriction protocol in Lieber's study. Furthermore, body weight gains in either ad libitum or dietary restricted feeding, and associated fatty changes were reproduced in a later study published in Journal of Hepatology [[3]Lieber C.S. Decarli L.M. Leo M.A. Mak K.M. Ponomarenko A. Ren C. et al.Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH.J Hepatol. 2008; 48: 318-326Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. It is imperative that Marsman et al. reassess the liquid diet feeding methodology to ensure that both caloric intake and gains in body weight are equivalent to those described by Lieber et al. [2Lieber C.S. Leo M.A. Mak K.M. Xu Y. Cao Q. Ren C. et al.Model of nonalcoholic steatohepatitis.Am J Clin Nutr. 2004; 79: 502-509Crossref PubMed Scopus (361) Google Scholar, 3Lieber C.S. Decarli L.M. Leo M.A. Mak K.M. Ponomarenko A. Ren C. et al.Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH.J Hepatol. 2008; 48: 318-326Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Until then it is presumptuous to conclude that the Lieber–Decarli high-fat diet model is not reproducible for the pathogenesis of hepatosteatosis in rats.