Dietary cholesterol supplementation to a plant-based diet suppresses the complete pathway of cholesterol synthesis and induces bile acid production in Atlantic salmon (Salmo salar L.)

Plants now supply more than 50 % of protein in Norwegian salmon aquafeeds. The inclusion of plant protein in aquafeeds may be associated with decreased lipid digestibility and cholesterol and bile salt levels, indicating that the replacement of fishmeal with plant protein could result in inadequate supplies of cholesterol in fish. A reduction in feed efficiency, fish growth and pathogen resistance is often observed in parallel to alterations in sterol metabolism. Previous studies have indicated that the negative effects induced by plant components can be attenuated when diets are supplemented with cholesterol. The present study evaluated the effects of dietary cholesterol supplementation (1·5 %) in Atlantic salmon fed a plant-based diet for 77 d. The weights of body, intestines and liver were recorded and blood, tissues, faeces, chyme and bile were sampled for the evaluation of effects on growth, nutrient utilisation and metabolism, and transcriptome and metabolite levels, with particular emphasis on sterol metabolism and organ structure and function. Cholesterol supplementation did not affect the growth or organ weights of Atlantic salmon, but seemed to promote the induction of cholesterol and plant sterol efflux in the intestine while suppressing sterol uptake. Cholesterol biosynthesis decreased correspondingly and conversion into bile acids increased. The marked effect of cholesterol supplementation on bile acid synthesis suggests that dietary cholesterol can be used to increase bile acid synthesis in fish. The present study clearly demonstrated how Atlantic salmon adjusted their metabolic functions in response to the dietary load of cholesterol. It has also expanded our understanding of sterol metabolism and turnover, adding to the existing, rather sparse, knowledge of these processes in fish.

[1]  E. Arenas Faculty Opinions recommendation of Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. , 2015 .

[2]  T. Kortner,et al.  Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation, lipoprotein and sterol metabolism in Atlantic salmon (Salmo salar L.) – CORRIGENDUM , 2014, British Journal of Nutrition.

[3]  G. Rosenlund,et al.  High levels of dietary phytosterols affect lipid metabolism and increase liver and plasma TAG in Atlantic salmon (Salmo salar L.). , 2013, The British journal of nutrition.

[4]  T. Kortner,et al.  Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salar L.) , 2013, British Journal of Nutrition.

[5]  Xi Zhang,et al.  Improving the growth performance and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal-based diets using dietary cholesterol supplementation. , 2013, The British journal of nutrition.

[6]  L. Ross,et al.  Nutritional evaluation of autoclaved Salicornia bigelovii Torr. seed meal supplemented with varying levels of cholesterol on growth, nutrient utilization and survival of the Nile tilapia (Oreochromis niloticus) , 2013, Aquaculture International.

[7]  T. Kortner,et al.  Transcriptional regulation of cholesterol and bile acid metabolism after dietary soyabean meal treatment in Atlantic salmon (Salmo salar L.). , 2013, The British journal of nutrition.

[8]  J. G. Bell,et al.  Hepatic transcriptome analysis of inter-family variability in flesh n-3 long-chain polyunsaturated fatty acid content in Atlantic salmon , 2012, BMC Genomics.

[9]  L. Goedeke,et al.  Regulation of cholesterol homeostasis , 2012, Cellular and Molecular Life Sciences.

[10]  Wei Xu,et al.  Synergistic effects of dietary cholesterol and taurine on growth performance and cholesterol metabolism in juvenile turbot (Scophthalmus maximus L.) fed high plant protein diets , 2012 .

[11]  L. Bargelloni,et al.  Effects of the total replacement of fish-based diet with plant-based diet on the hepatic transcriptome of two European sea bass (Dicentrarchus labrax) half-sibfamilies showing different growth rates with the plant-based diet , 2011, BMC Genomics.

[12]  I. Navarro,et al.  Regulation of LXR by fatty acids, insulin, growth hormone and tumor necrosis factor-α in rainbow trout myocytes. , 2011, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[13]  Wei Xu,et al.  Effects of dietary cholesterol on growth performance, feed intake and cholesterol metabolism in juvenile turbot (Scophthalmus maximus L.) fed high plant protein diets , 2011 .

[14]  S. Arata,et al.  Dietary Cholesterol Reduces Plasma Triacylglycerol in Apolipoprotein E-Null Mice: Suppression of Lipin-1 and -2 in the Glycerol-3-Phosphate Pathway , 2011, PloS one.

[15]  T. Kortner,et al.  Candidate reference genes for quantitative real-time PCR (qPCR) assays during development of a diet-related enteropathy in Atlantic salmon (Salmo salar L.) and the potential pitfalls of uncritical use of normalization software tools , 2011 .

[16]  Gerrit Timmerhaus,et al.  Development and assessment of oligonucleotide microarrays for Atlantic salmon (Salmo salar L.). , 2011, Comparative biochemistry and physiology. Part D, Genomics & proteomics.

[17]  Å. Krogdahl,et al.  Important antinutrients in plant feedstuffs for aquaculture: an update on recent findings regarding responses in salmonids , 2010 .

[18]  A. Farrell,et al.  Feeding aquaculture in an era of finite resources , 2009, Proceedings of the National Academy of Sciences.

[19]  Jure Acimovic,et al.  Combined gas chromatographic/mass spectrometric analysis of cholesterol precursors and plant sterols in cultured cells. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[20]  Wenbing Zhang,et al.  Interactive effects of dietary cholesterol and protein sources on growth performance and cholesterol metabolism of Japanese flounder (Paralichthys olivaceus) , 2009 .

[21]  V. Beneš,et al.  The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. , 2009, Clinical chemistry.

[22]  F. Blanco-Vaca,et al.  New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. , 2009, Atherosclerosis.

[23]  D. Tocher,et al.  Atlantic salmon (Salmo salar) postsmolts adapt lipid digestion according to elevated dietary wax esters from Calanus finmarchicus. , 2009 .

[24]  J. G. Bell,et al.  The role of phospholipids in nutrition and metabolism of teleost fish , 2008 .

[25]  D. Tocher,et al.  Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar) , 2008, BMC Genomics.

[26]  P. Howles,et al.  Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[27]  L. Mydland,et al.  Lipid digestibility, bile drainage and development of morphological intestinal changes in rainbow trout (Oncorhynchus mykiss) fed diets containing defatted soybean meal , 2008 .

[28]  Elina Ikonen,et al.  Cellular cholesterol trafficking and compartmentalization , 2008, Nature Reviews Molecular Cell Biology.

[29]  J. Wahren,et al.  Novel LC-MS/MS method for assay of 7alpha-hydroxy-4-cholesten-3-one in human plasma. Evidence for a significant extrahepatic metabolism. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[30]  K. Dąbrowski,et al.  Expanding the utilization of sustainable plant products in aquafeeds: a review , 2007 .

[31]  D. Q. Wang Regulation of intestinal cholesterol absorption. , 2007, Annual review of physiology.

[32]  K. Eder,et al.  Activation of PPARalpha lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. , 2007, Biochemical pharmacology.

[33]  Takeshi Yamamoto,et al.  Supplemental effect of bile salts to soybean meal-based diet on growth and feed utilization of rainbow trout Oncorhynchus mykiss , 2007, Fisheries Science.

[34]  P. Tso,et al.  CD36 is important for chylomicron formation and secretion and may mediate cholesterol uptake in the proximal intestine. , 2006, Gastroenterology.

[35]  S. Satoh,et al.  Disease resistance and hypocholesterolemia in yellowtail Seriola quinqueradiata fed a non-fishmeal diet , 2006, Fisheries Science.

[36]  Albert K Groen,et al.  Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. , 2006, The Journal of clinical investigation.

[37]  D. Mangelsdorf,et al.  LXRS and FXR: the yin and yang of cholesterol and fat metabolism. , 2006, Annual review of physiology.

[38]  B. Angelin,et al.  Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel‐filtration system , 2006, European journal of clinical investigation.

[39]  Joseph L. Goldstein,et al.  Protein Sensors for Membrane Sterols , 2006, Cell.

[40]  Jianjun Liu,et al.  Niemann-Pick C1 Like 1 (NPC1L1) Is the Intestinal Phytosterol and Cholesterol Transporter and a Key Modulator of Whole-body Cholesterol Homeostasis* , 2004, Journal of Biological Chemistry.

[41]  D. Houlihan,et al.  Dietary plant-protein substitution affects hepatic metabolism in rainbow trout (Oncorhynchus mykiss). , 2004, The British journal of nutrition.

[42]  R. Twibell,et al.  Preliminary evidence that cholesterol improves growth and feed intake of soybean meal-based diets in aquaria studies with juvenile channel catfish, Ictalurus punctatus , 2004 .

[43]  B. Casetta,et al.  Quantitative Analysis of Bile Acids in Human Plasma by Liquid Chromatography-Electrospray Tandem Mass Spectrometry: A Simple and Rapid One-Step Method , 2003, Clinical chemistry and laboratory medicine.

[44]  Å. Krogdahl,et al.  Effects of graded levels of standard soybean meal on intestinal structure, mucosal enzyme activities, and pancreatic response in Atlantic salmon (Salmo salar L.) , 2003 .

[45]  D. Russell The enzymes, regulation, and genetics of bile acid synthesis. , 2003, Annual review of biochemistry.

[46]  B. Angelin,et al.  Differences in the Regulation of the Classical and the Alternative Pathway for Bile Acid Synthesis in Human Liver , 2002, The Journal of Biological Chemistry.

[47]  Joseph L Goldstein,et al.  SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. , 2002, The Journal of clinical investigation.

[48]  R. Zechner,et al.  Inactive Lipoprotein Lipase (LPL) Alone Increases Selective Cholesterol Ester Uptake in Vivo, Whereas in the Presence of Active LPL It Also Increases Triglyceride Hydrolysis and Whole Particle Lipoprotein Uptake* , 2002, The Journal of Biological Chemistry.

[49]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[50]  H. Sone,et al.  Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis. , 2001, Biochemical and Biophysical Research Communications - BBRC.

[51]  K. Becker,et al.  Antinutritional factors present in plant-derived alternate fish feed ingredients and their effects in fish , 2001 .

[52]  W. Sealey,et al.  Dietary cholesterol and lecithin have limited effects on growth and body composition of hybrid striped bass (Morone chrysops × M. saxatilis) , 2001 .

[53]  D. Mangelsdorf,et al.  Nuclear receptor regulation of cholesterol and bile acid metabolism. , 1999, Current opinion in biotechnology.

[54]  S. Kaushik,et al.  Partial or total replacement of fish meal by corn gluten meal in diet for turbot (Psetta maxima) , 1999 .

[55]  Storebakken,et al.  Cholesterol and short‐chain fatty acids in diets for Atlantic salmon Salmo salar (L.): effects on growth, organ indices, macronutrient digestibility, and fatty acid composition , 1999 .

[56]  N. Okamoto,et al.  Correlation Between Plasma Component Levels of Cultured Fish and Resistance to Bacterial Infection , 1998 .

[57]  R. Hammer,et al.  Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXRα , 1998, Cell.

[58]  T. Storebakken,et al.  Adaptation to soybean meal in diets for rainbow trout, Oncorhynchus mykiss , 1997 .

[59]  J. Goldstein,et al.  The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor , 1997, Cell.

[60]  J. Cravedi,et al.  Partial or total replacement of fish meal by soybean protein on growth, protein utilization, potential estrogenic or antigenic effects, cholesterolemia and flesh quality in rainbow trout, Oncorhynchus mykiss , 1995 .

[61]  U. Diczfalusy,et al.  Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. , 1995, Analytical biochemistry.

[62]  J. Cuthbert,et al.  Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7 alpha-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme A reductase or low density lipoprotein receptor. , 1992, The Journal of biological chemistry.

[63]  K. Einarsson,et al.  The plasma level of 7α‐hydroxy‐4‐cholesten‐3‐one reflects the activity of hepatic cholesterol 7α‐hydroxylase in man , 1991 .

[64]  W. Keung,et al.  Human liver alcohol dehydrogenases catalyze the oxidation of the intermediary alcohols of the shunt pathway of mevalonate metabolism. , 1991, Biochemical and biophysical research communications.

[65]  I. Björkhem,et al.  Determination of serum levels of unesterified lanosterol by isotope dilution-mass spectrometry. , 1990, Scandinavian journal of clinical and laboratory investigation.

[66]  H. Kempen,et al.  Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans. , 1988, Journal of lipid research.

[67]  H. Brunengraber,et al.  The shunt pathway of mevalonate metabolism in the isolated perfused rat kidney. , 1984, The Journal of biological chemistry.

[68]  I. Björkhem,et al.  Assay of the major bile acids in serum by isotope dilution-mass spectrometry. , 1983, Scandinavian journal of clinical and laboratory investigation.

[69]  A. Kuksis,et al.  Bile acid composition of rainbow trout,Salmo gairdneri , 1974, Lipids.

[70]  Y. Kishimoto,et al.  Esterification of fatty acids at room temperature by chloroform-methanolic HCl-cupric acetate. , 1973, Journal of lipid research.

[71]  G. Waller,et al.  Dimethoxypropane Induced Transesterification of Fats and Oils in Preparation of Methyl Esters for Gas Chromatographic Analysis. , 1964 .

[72]  Xi Zhang,et al.  Effects of dietary cholesterol on antioxidant capacity, non-specific immune response, and resistance to Aeromonas hydrophila in rainbow trout (Oncorhynchus mykiss) fed soybean meal-based diets. , 2013, Fish & shellfish immunology.

[73]  M. Metian,et al.  Demand and supply of feed ingredients for farmed fish and crustaceans : trends and prospects , 2011 .

[74]  G.,et al.  Differential gene expression after total replacement of dietary fish meal and fish oil by plant products in rainbow trout ( Oncorhynchus mykiss ) liver , 2009 .

[75]  X Yu,et al.  J.Chromatogr., B: Anal. Technol. Biomed. Life Sci. , 2004 .

[76]  K. Einarsson,et al.  The plasma level of 7 alpha-hydroxy-4-cholesten-3-one reflects the activity of hepatic cholesterol 7 alpha-hydroxylase in man. , 1991, FEBS letters.

[77]  E. Lund,et al.  Determination of serum levels of unesterified lathosterol by isotope dilution-mass spectrometry. , 1989, Scandinavian journal of clinical and laboratory investigation.

[78]  H. Brunengraber,et al.  The shunt pathway of mevalonate metabolism in the isolated perfused rat liver. , 1984, Journal of Biological Chemistry.

[79]  A. Tall,et al.  Plasma cholesteryl ester transfer protein. , 1993, Journal of lipid research.