Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

Lipids in Health and Disease

Alicia Leikin-Frenkel²  Amiram Raz¹  Limor Shomonov-Wagner¹ 

[1] G.S.W. Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel;Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Israel

关键词: Insulin resistance;    Programming;    Fatty acids/desaturases;    Lipids;    Liver;    Nutrition;    Saturated fatty acids;    Omega (ω) -3 fatty acids;    Maternal diet;   

Others  :  1132831
DOI  :  10.1186/s12944-015-0012-7

 received in 2015-01-06, accepted in 2015-02-13,  发布年份 2015

【 摘 要 】

Background

Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning.

Methods

3 month old C57Bl6/J female mice were fed diets containing normal amount of calories but rich in SFA alone or partially replaced with ALA, DHA or EPA before mating, during pregnancy and lactation.

Results

Pregnant mice fed SFA produced offspring with the highest HOMA index, liver lipids and desaturase activities. ALA prevented SFA induced lipid increase but DHA and EPA only reduced it by 42% and 31% respectively. ALA, DHA and EPA decreased HOMA index by 84%, 75% and 83% respectively. ALA, DHA and EPA decreased Δ6 and SCD1 desaturase activities about 30%.

Conclusions

SFA feeding to mothers predisposes their offspring to develop IR and liver lipid accumulation already at weaning. ω3 fatty acids reduce IR, ALA halts lipid accumulation whereas DHA and EPA only blunt it.ALA and DHA restore the increased SCD1 to normal. These studies suggest that ω-3 fatty acids have different potencies to preclude lipid accumulation in the offspring partially by affecting pathways associated to SCD1 modulation.

【 授权许可】

   
2015 Shomonov-Wagner et al.; licensee BioMed Central.

【 图 表 】

Figure 3.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]James PT, Rigbi N, Leach R: The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004, 11:3-8.
• [2]McAllister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger J, Baskin M, et al.: Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 2009, 49:868-913.
• [3]Vallim T, Salter AM: Regulation of hepatic gene expression by saturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 2010, 82:211-218.
• [4]Halberg N, Wernstedt-Asterholm I, Scherer PE: The adipocyte as an endocrine cell. Endocrinol Metab Clin North Am 2008, 37:753-768.
• [5]Hughes AN, Oxford JT: A lipid-rich gestational diet predisposes offspring to nonalcoholic fatty liver disease: a potential sequence of events. Hepat Med 2014, 6:15-23.
• [6]Lottenberg AM, Afonso Mda S, Lavrador MS, Machado RM, Nakandakare ER: The role of dietary fatty acids in the pathology of metabolic syndrome. J Nutr Biochem 2012, 23:1027-1040.
• [7]Stryjecki C, Mutch DM: Fatty acid-gene interactions, adipokines and obesity. Eur J Clin Nutr 2011, 65:285-297.
• [8]Afman LA, Muller M: Human nutrigenomics of gene regulation by dietary fatty acids. Prog Lipid Res 2012, 51:63-70.
• [9]Burr GO, Burr MM: The nature and role of the fatty acids essential in nutrition. J Biol Chem 1930, 86:587-621.
• [10]Carpentier YA, Portois L, Malaisse WJ: n−3 Fatty acids and the metabolic syndrome. Am J Clin Nutr 2006, 83:S1499-1504S.
• [11]Tontonoz P, Spiegelman BM: Fat and beyond: the diverse biology of PPAR gamma. Annu Rev Plant Physiol Plant Mol Biol 2008, 77:289-331.
• [12]Bruce KD, Hanson MA: The developmental origins, mechanisms and implication of metabolic syndrome. J Nutr 2010, 140:648-652.
• [13]Barker DJ, Osmond C, Law CM: The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. J Epidemiol Community Health 1989, 43:237-240.
• [14]Bouret SG: Early life origins of obesity: role of hypothalamic programming. J Pediatr Gastroenterol Nutr 2009, 48:531-538.
• [15]Deckelbaum RJ, Torrejon C: The Omega-3 fatty acid nutritional landscape: health benefits and sources. J Nutr 2012, 142:587S-591S.
• [16]Das UN: A defect in the activity of Δ6 and Δ5 desaturases may be a factor predisposing to the development of insulin resistance syndrome. Prostaglandins Leukot Essent Fat Acids 2005, 72:343-350.
• [17]Waters KM, Ntambi JM: Polyunsaturated fatty acids inhibit hepatic stearoyl-CoA desaturase-1 gene in diabetic mice. Lipids 1996, 31:S33-S36.
• [18]Gilat T, Leikin-Frenkel A, Goldiner I, Juhel C, Lafont H, Gobbi D, et al.: Prevention of diet induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC). Hepatology 2003, 38:436-442.
• [19]Sartore G, Lapolla A, Reitano R, Zambon S, Romanato G, Marin R, et al.: Desaturase activities and metabolic control in type 2 diabetes. Prostaglandins Leukot Essent Fat Acids 2008, 79:55-58.
• [20]Sampath H, Miyazaki M, Dobrzyn A, Ntambi JM: Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem 2007, 282:2483-2493.
• [21]Demmelmair HH, Rosen JV, Koletzko B: Long-term consequences of early nutrition. Early Hum Dev 2006, 82:56-574.
• [22]Symonds ME, Sebert SP, Hyatt MA, Budge H: Nutritional programming of the metabolic syndrome. Nature Rev Endocrin 2009, 5:604-610.
• [23]Innis SM: Essential fatty acid transfer and foetal development. Placenta 2005, 26:570-575.
• [24]Hornstra G: Essential fatty acids in mothers and their neonates. Am J Clin Nutr 2000, 71:1262S-1269S.
• [25]Vaisman N, Leikin-Frenkel A: Lipid supplemented diet given to rats during pregnancy enhances the level of Δ6 desaturase mRNA level in liver of developing embryos. Clin Nutr 2003, 1:22.
• [26]Hussain A, Nookaew I, Khoomrung S, Andersson L, Larsson I, Hulthén L, et al.: A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post-weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice. Acta Physiol 2013, 209:220-234.
• [27]Heerwagen MJR, Stewart MS, de la Houssaye BA, Janssen RC, Friedman JE: Transgenic increase in N-3/N-6 Fatty acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice. PLoS One 2013, 8(6):e67791. doi:10.1371/journal.pone.0067791
• [28]Hollander KS, Tempel Brami C, Konikoff FM, Fainaru M, Leikin-Frenkel A: Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice. Arch Physiol Biochem 2014, 120:99-111.
• [29]Chechi K, Cheema SK: Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice. Exp Clin Cardiol 2006, 11:129-135.
• [30]Lee JS, Pinnamaneni SK, Eo SJ, Cho IH, Pyo JH, Chang KK, et al.: Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol 2006, 100:1467-1474.
• [31]Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW: Influence of dietary fat composition on development of insulin resistance in rats: relationship to muscle triglyceride and ω-3 fatty acids in muscle phospholipid. Diabetes 1991, 40:280-289.
• [32]Gentile CL, Frye MA, Pagliassotti MJ: Fatty acids and the endoplasmic reticulum in non-alcoholic fatty liver disease. Biofactors 2011, 37:8-16.
• [33]Leamy AK, Egnatchik RA, Young JD: Molecular Mechanisms and the Role of Saturated Fatty Acids in the Progression of Non-Alcoholic Fatty Liver Disease. Prog Lipid Res 2013, 52:165-174.
• [34]Browning JD, Horton JD: Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004, 114:147-152.
• [35]Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, et al.: Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A 2011, 108:16381-16385.
• [36]Lorente-Cebrián S, Costa AGV, Navas-Carretero S, Zabala M, Martínez JA, Moreno-Aliaga MJ: Role of omega-3 fatty acids in obesity, metabolic syndrome and cardiovascular diseases: a review of the evidence. J Physiol Biochem 2013, 69:633-651.
• [37]Jump DB: Fatty acid regulation of hepatic lipid metabolism. Curr Opin Clin Nutr Metab Care 2011, 14:115-120.
• [38]Brown JM, Chung S, Sawyer JK, Degirolamo C, Alger HM, Nguyen TM, et al.: Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 (SCD1) inhibition prevents the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2010, 30:24-30.
• [39]Poudyal H, Panchal SK, Waanders Ward JL, Brown L: Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats. J Nutr Biochem 2012, 23:153-162.
• [40]Panchal SK, Ward LC, Brown L: Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. J Nutr Biochem 2013, 24:1041-1052.
• [41]Prince E, Lazare FB, Treem WR, Xu J, Iqbal J, Pan X, et al.: ω-3 fatty acids prevent hepatic steatosis, independent of ppar-α activity, in a murine model of parenteral nutrition–associated liver disease. J Parenter Enteral Nutr 2013, 38:308-616.
• [42]Grønn M, Christensen E, Hagve TA, Christophersen BO: Peroxisomal retroconversion of docosahexaenoic acid (22:6 (n-3)) to eicosapentaenoic acid (20:5 (n-3)) studied in isolated rat liver cells. Biochim Biophys Acta 1991, 1081:85-91.
• [43]Anderson BM, Ma DWL: Are all n-3 polyunsaturated fatty acids created equal? Lipids Health Dis 2009, 8:33. BioMed Central Full Text
• [44]Flowers MT, Ntambi JM: Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol 2008, 19:248-256.
• [45]Das UN: A defect in the activities of Δ6 and Δ5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease World J. Diabetes 2011, 2:176-188.
• [46]Shaw B, Lambert S, Wong MH, Ralston JC, Stryjecki C, Mutch DM: Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes. J Nutrigenet Nutrigenomics 2013, 6:1-15.
• [47]Jump DB, Botolin D, Wanga Y, Xua J, Demeure O, Christiana B: Docosahexaenoic acid (DHA) and hepatic gene transcription_Chemistry and Physics of. Lipids 2008, 153:3-13.
• [48]Monteiro J, Leslie M, Moghadasian MH, Arendt BN, Allard JP, Ma DWL: The role of n _ 6 and n _ 3 polyunsaturated fatty acids in the manifestation of the metabolic syndrome in cardiovascular disease and nonalcoholic fatty liver disease. Food Funct 2014, 5:426.
• [49]Merino DM, Ma DWL, Mutch DM: Genetic variation in lipid desaturases and its impact on the development of human disease. Lipids Health Dis 2010, 9:63. BioMed Central Full Text
• [50]Simopoulos AP: Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk. Exp Biol Med 2010, 235:785-795.
• [51]Schwenk RW, Jonas W, Ernst SB, Kammel A, Jahnert P: Diet-dependent alterations of hepatic Scd1 expression are accompanied by differences in promoter methylation. Horm Metab Res 2013, 45:786-794.
• [52]Kalaany NY, Gauthier KC, Zavacki AM, Mammen PPA, Kitazume T, Peterson JA, et al.: LXRs regulate the balance between fat storage and oxidation. Cell Metab 2005, 1:231-244.
• [53]Calder PC: Mechanisms of Action of (n-3) fatty acids. J Nutr 2012, 142:592S-599S.
• [54]Leikin AI, Shinitzky M: Characterization of lipids surrounding Δ6 desaturase of rat liver microsomes. Biochim Biophys Acta 1995, 1256:13-17.
• [55]Kohli P, Levy BD: Resolvins and protectins: mediating solutions to inflammation. Brit J Pharm 2009, 158:971-960.
• [56]Folch J, And Sloane Stanley GH LM: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
• [57]Mehlem A, Hagberg CE, Muhl L, Eriksson U, Falkevall A: Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease. Nat Protocols 2013, 8:1149-54.
• [58]Warensjö E, Sundström J, Vessby B, Cederholm T, Risérus U: Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study 1, 2, 3. Am J Clin Nutr 2008, 88:203-209.