Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Maternal High Fat Diet and its Expressions in the Heart and Liver in the Mice Embryogenesis

Author(s): Sanjeev Nirala*, Xue-Rui Tan, Muhammad Shafiq, Rajesh Basnet and Apekshya Singh

Volume 24, Issue 7, 2024

Published on: 28 August, 2023

Page: [889 - 898] Pages: 10

DOI: 10.2174/1566524023666230605142119

Price: $65

Abstract

Background: The developmental biology for the nonalcoholic fatty liver disease and coronary heart disease are known but elaborative ideas of triglycerides phenomenon in the embryo-genesis of the liver and the heart are still not clear.

Objective: The aim of the study was to relate different triglycerides like LXRα, LPL, LDL R, PPARG-, SREBP-1C expression in the high fat fed mice with the normal fed diet mice in the process of developmental and embryo-genesis biology.

Methods: Tissue preparation was done by ripalysis. Different protein content was obtained via western blot for the 6 samples namely a-17.5 days mice embryo heart; b- 0th day or the birthday mice infant heart; c-1 week mice infant heart; d-2 weeks mice infant heart; e-3 weeks mice infant heart; f-Adult mice heart. Protein lysates from the heart tissues of the mice was obtained via homegenization and centrifugation. Hematoxylin and Eosin (H and E) was done to see the fat droplets in the liver tissues at the different developmental stages.

Result: LXRα,SREBP-1C expression in 17.5 days mice embryo heart and 0th day or the birthday mice infant heart is highly expressed in the high fat diet. LDL-R in the high fat diet mice is increased in 2 weeks mice infant heart but in17.5 days mice embryo heart and in 0th day or the birthday mice infant heart it is low expression but from 1week mice infant heart to the adult mice heart the expression is in decreasing trend. Similarly LPL is highly expressed in17.5 days mice embryo heart and 1 week mice infant heart and thus low expression in decreasing order until adult mice heart.Thus, these results collectively shows that maternal HF diet increases expression of proteins such as LPL, LDLr in the embryo phase and thus getting normal expressions in the adult phase that facilitate Triglycerides (TAG) hydrolysis across the liver and the heart. Also,maternal high fat diet increases the SREBP1c expression, leading to stimulation of LPL Expression.

Conclusion: In summary, using a pregnant mice model, we found that maternal high fat diet increases the fetal fat accumulation. Elevated placental LPL activity and expression of genes that facilitate placental lipid transport suggest that enhanced placental lipid transport may play a key role in maternal nutrition and obesity-induced fetal fat accumulation.

« Previous Next »
[1]
Stergios A. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019; 92: 82-97.
[http://dx.doi.org/10.1016/j.metabol.2018.11.014]
[2]
Olivecrona T, Bengtsson-Olivecrona G. Lipoprotein lipase and hepatic lipase. Curr Opin Lipidol 1993; 4(3): 187-96.
[http://dx.doi.org/10.1097/00041433-199306000-00003]
[3]
Wion KL, Kirchgessner TG, Lusis AJ, Schotz MC, Lawn RM. Human lipoprotein lipase complementary DNA sequence. Science 1987; 235(4796): 1638-41.
[http://dx.doi.org/10.1126/science.3823907] [PMID: 3823907]
[4]
Zechner R, Newman TC, Steiner E, Breslow JL. The structure of the mouse lipoprotein lipase gene: A B1 repetitive element is inserted into the 3′ untranslated region of the mRNA. Genomics 1991; 11(1): 62-76.
[http://dx.doi.org/10.1016/0888-7543(91)90102-K] [PMID: 1765386]
[5]
Eisenberg S. High density lipoprotein metabolism. J Lipid Res 1984; 25(10): 1017-58.
[http://dx.doi.org/10.1016/S0022-2275(20)37713-0] [PMID: 6392459]
[6]
Brunzell JD. Familial lipoprotein lipase deficiency and other causes of chylomicronemia syndromesThe Metabolic Basis of Inherited Disease. New York: McGraw Hill 1995; pp. 1913-32.
[7]
Goldberg IJ, Le NA, Ginsberg HN, Krauss RM, Lindgren FT. Lipoprotein metabolism during acute inhibition of lipoprotein lipase in the cynomolgus monkey. J Clin Invest 1988; 81(2): 561-8.
[http://dx.doi.org/10.1172/JCI113354] [PMID: 3276735]
[8]
Paterniti JR Jr, Brown WV, Ginsberg HN, Artzt K. Combined lipase deficiency (cld): A lethal mutation on chromosome 17 of the mouse. Science 1983; 221(4606): 167-9.
[http://dx.doi.org/10.1126/science.6857276] [PMID: 6857276]
[9]
Masuno H, Blanchette-Mackie EJ, Chernick SS, Scow RO. Synthesis of inactive nonsecretable high mannose-type lipoprotein lipase by cultured brown adipocytes of combined lipase-deficient cld/cld mice. J Biol Chem 1990; 265(3): 1628-38.
[http://dx.doi.org/10.1016/S0021-9258(19)40063-X] [PMID: 2104849]
[10]
Harlan WR Jr, Winesett PS, Wasserman AJ. Tissue lipoprotein lipase in normal individuals and in individuals with exogenous hypertriglyceridemia and the relationship of this enzyme to assimilation of fat. J Clin Invest 1967; 46(2): 239-47.
[http://dx.doi.org/10.1172/JCI105526] [PMID: 6018761]
[11]
Miesenböck G, Hölzl B, Föger B, et al. Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. J Clin Invest 1993; 91(2): 448-55.
[http://dx.doi.org/10.1172/JCI116222] [PMID: 8432854]
[12]
Wilson DE, Emi M, Iverius PH, et al. Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation. J Clin Invest 1990; 86(3): 735-50.
[http://dx.doi.org/10.1172/JCI114770] [PMID: 2394828]
[13]
Ma Y, Liu MS, Ginzinger D, Frohlich J, Brunzell JD, Hayden MR. Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172-->Cys mutation in the lipoprotein lipase gene. J Clin Invest 1993; 91(5): 1953-8.
[http://dx.doi.org/10.1172/JCI116414] [PMID: 8486765]
[14]
Williams RR, Hopkins PN, Hunt SC, et al. Familial dyslipidaemic hypertension and other multiple metabolic syndromes. Ann Med 1992; 24(6): 469-75.
[http://dx.doi.org/10.3109/07853899209166998] [PMID: 1485941]
[15]
Babirak SP, Brown BG, Brunzell JD. Familial combined hyperlipidemia and abnormal lipoprotein lipase. Arterioscler Thromb 1992; 12(10): 1176-83.
[http://dx.doi.org/10.1161/01.ATV.12.10.1176] [PMID: 1390589]
[16]
Gagné E, Genest J Jr, Zhang H, Clarke LA, Hayden MR. Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia. Arterioscler Thromb 1994; 14(8): 1250-7.
[http://dx.doi.org/10.1161/01.ATV.14.8.1250] [PMID: 8049185]
[17]
Nevin DN, Brunzell JD, Deeb SS. The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity. Arterioscler Thromb 1994; 14(6): 869-73.
[http://dx.doi.org/10.1161/01.ATV.14.6.869] [PMID: 8199176]
[18]
Shimada M, Shimano H, Gotoda T, et al. Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet-induced hypertriglyceridemia and hypercholesterolemia. J Biol Chem 1993; 268(24): 17924-9.
[http://dx.doi.org/10.1016/S0021-9258(17)46793-7] [PMID: 8349676]
[19]
Liu MS, Jirik FR, LeBoeuf RC, et al. Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. J Biol Chem 1994; 269(15): 11417-24.
[http://dx.doi.org/10.1016/S0021-9258(19)78140-X] [PMID: 8157673]
[20]
Zsigmond E, Scheffler E, Forte TM, Potenz R, Wu W, Chan L. Transgenic mice expressing human lipoprotein lipase driven by the mouse metallothionein promoter. A phenotype associated with increased perinatal mortality and reduced plasma very low density lipoprotein of normal size. J Biol Chem 1994; 269(29): 18757-66.
[http://dx.doi.org/10.1016/S0021-9258(17)32233-0] [PMID: 8034629]
[21]
Gofman JW, DeLalla O, Flazier F, et al. The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis, and coronary disease. Plasma 1954; 2: 413-83.
[22]
Albrink M, Mann E. Serum triglycerides in coronary artery disease. Arch Intern Medbronary heart disease. N Engl J Med 1980; 302: 1383-9.
[23]
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: A meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 3(2): 213-9.
[http://dx.doi.org/10.1097/00043798-199604000-00014] [PMID: 8836866]
[24]
Abdel-Maksoud MF, Hokanson JE. The complex role of triglyceride in cardiovascular disease: Both independence and synergy with HDL cholesterol. Semin Vasc Med 2002; 2(3): 325-3.
[25]
Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Triglyceride concentration and ischemic heart disease: An eight-year follow-up in the Copenhagen male study. Circulation 1998; 97(11): 1029-36.
[http://dx.doi.org/10.1161/01.CIR.97.11.1029]
[26]
Friis CM, Qvigstad E, Paasche Roland MC, et al. Newborn body fat: Associations with maternal metabolic state and placental size. PLoS One 2013; 8(2): e57467.
[http://dx.doi.org/10.1371/journal.pone.0057467] [PMID: 23460863]
[27]
Gernand AD, Christian P, Paul RR, et al. Maternal weight and body composition during pregnancy are associated with placental and birth weight in rural Bangladesh. J Nutr 2012; 142(11): 2010-6.
[http://dx.doi.org/10.3945/jn.112.163634] [PMID: 22990469]
[28]
Lindegaard MLS, Olivecrona G, Christoffersen C, et al. Endothelial and lipoprotein lipases in human and mouse placenta. J Lipid Res 2005; 46(11): 2339-46.
[http://dx.doi.org/10.1194/jlr.M500277-JLR200] [PMID: 16150822]
[29]
Bonet B, Brunzell JD, Gown AM, Knopp RH. Metabolism of very-low-density lipoprotein triglyceride by human placental cells: The role of lipoprotein lipase. Metabolism 1992; 41(6): 596-603.
[http://dx.doi.org/10.1016/0026-0495(92)90051-B] [PMID: 1640846]
[30]
Bansal N, Cruickshank JK, McElduff P, Durrington PN. Cord blood lipoproteins and prenatal influences. Curr Opin Lipidol 2005; 16(4): 400-8.
[http://dx.doi.org/10.1097/01.mol.0000174154.61307.16] [PMID: 15990588]
[31]
Dubé E, Gravel A, Martin C, et al. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta. Biol Reprod 2012; 87(1): 14-, 1-1.
[http://dx.doi.org/10.1095/biolreprod.111.098095] [PMID: 22553224]
[32]
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.
[http://dx.doi.org/10.1371/journal.pone.0067791] [PMID: 23825686]
[33]
Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15(19): 5336-48.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00918.x] [PMID: 8895578]
[34]
Zhu MJ, Ma Y, Long NM, Du M, Ford SP. Maternal obesity markedly increases placental fatty acid transporter expression and fetal blood triglycerides at midgestation in the ewe. Am J Physiol Regul Integr Comp Physiol 2010; 299(5): R1224-31.
[http://dx.doi.org/10.1152/ajpregu.00309.2010] [PMID: 20844260]
[35]
Taskinen MR, Nikkilä EA. Effects of caloric restriction on lipid metabolism in man changes of tissue lipoprotein lipase activities and of serum lipoproteins. Atherosclerosis 1979; 32(3): 289-99.
[http://dx.doi.org/10.1016/0021-9150(79)90172-2] [PMID: 223589]
[36]
Taskinen MR, Nikkilä EA. Basal and postprandial lipoprotein lipase activity in adipose tissue during caloric restriction and refeeding. Metabolism 1987; 36(7): 625-30.
[http://dx.doi.org/10.1016/0026-0495(87)90144-2] [PMID: 3600276]
[37]
Xu F, Gao Z, Zhang J, et al. Lack of SIRT1 (Mammalian Sirtuin 1) activity leads to liver steatosis in the SIRT1+/- mice: A role of lipid mobilization and inflammation. Endocrinology 2010; 151(6): 2504-14.
[http://dx.doi.org/10.1210/en.2009-1013] [PMID: 20339025]
[38]
Shan TZ, Ren Y, Wu T, Liu CX, Wang YZ. Regulatory role of Sirt1 on the gene expression of fatty acid-binding protein 3 in cultured porcine adipocytes. J Cell Biochem 2009; 107(5): 984-91.
[http://dx.doi.org/10.1002/jcb.22203] [PMID: 19479941]
[39]
King V, Hibbert N, Seckl JR, Norman JE, Drake AJ. The effects of an obesogenic diet during pregnancy on fetal growth and placental gene expression are gestation dependent. Placenta 2013; 34(11): 1087-90.
[http://dx.doi.org/10.1016/j.placenta.2013.09.006] [PMID: 24090886]
[40]
Sferruzzi-Perri AN, Vaughan OR, Haro M, et al. An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J 2013; 27(10): 3928-37.
[http://dx.doi.org/10.1096/fj.13-234823] [PMID: 23825226]
[41]
Hayes EK, Lechowicz A, Petrik JJ, et al. Adverse fetal and neonatal outcomes associated with a life-long high fat diet: Role of altered development of the placental vasculature. PLoS One 2012; 7(3): e33370.
[http://dx.doi.org/10.1371/journal.pone.0033370] [PMID: 22442686]
[42]
King V, Dakin RS, Liu L, et al. Maternal obesity has little effect on the immediate offspring but impacts on the next generation. Endocrinology 2013; 154(7): 2514-24.
[http://dx.doi.org/10.1210/en.2013-1013] [PMID: 23696566]
[43]
Schaefer-Graf UM, Graf K, Kulbacka I, et al. Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 2008; 31(9): 1858-63.
[http://dx.doi.org/10.2337/dc08-0039] [PMID: 18606978]
[44]
Nolan CJ, Riley SF, Sheedy MT, Walstab JE, Beischer NA. Maternal serum triglyceride, glucose tolerance, and neonatal birth weight ratio in pregnancy. Diabetes Care 1995; 18(12): 1550-6.
[http://dx.doi.org/10.2337/diacare.18.12.1550] [PMID: 8722050]
[45]
Hwang J-Y, Choi HI, Kim H, et al. Relationship of maternal grain intake and serum triglyceride levels with infant birth weight: Mothers and Children’s Environmental Health (MOCEH) study. Eur J Clin Nutr 2015; 69(6): 676-80.
[46]
Laís VM, Oliveira JL, Morais CA, et al. Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem 2015; 26(2): 99-111.
[http://dx.doi.org/10.1016/j.jnutbio.2014.10.001]
[47]
Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol 2008; 59 (Suppl. 7): 31-55.
[PMID: 19258656]
[48]
Roberts CK, Vaziri ND, Liang KH, Barnard RJ. Reversibility of chronic experimental syndrome X by diet modification. Hypertension 2001; 37(5): 1323-8.
[http://dx.doi.org/10.1161/01.HYP.37.5.1323] [PMID: 11358948]
[49]
Barnard RJ, Faria DJ, Menges JE, Martin DA. Effects of a high-fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats. Atherosclerosis 1993; 100(2): 229-36.
[http://dx.doi.org/10.1016/0021-9150(93)90209-D] [PMID: 8357355]
[50]
Hulman S, Falkner B. The effect of excess dietary sucrose on growth, blood pressure, and metabolism in developing Sprague-Dawley rats. Pediatr Res 1994; 36(1 Pt 1): 95-100.
[http://dx.doi.org/10.1203/00006450-199407001-00017] [PMID: 7936845]
[51]
Dowman JK, Armstrong MJ, Tomlinson JW, Newsome PN. Current therapeutic strategies in non-alcoholic fatty liver disease. Diabetes Obes Metab 2011; 13(8): 692-702.
[http://dx.doi.org/10.1111/j.1463-1326.2011.01403.x] [PMID: 21449949]
[52]
Suganami T, Ogawa Y. Adipose tissue macrophages: Their role in adipose tissue remodeling. J Leukoc Biol 2010; 88(1): 33-9.
[http://dx.doi.org/10.1189/jlb.0210072] [PMID: 20360405]
[53]
Yang ZH, Miyahara H, Takeo J, Katayama M. Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetol Metab Syndr 2012; 4(1): 32.
[http://dx.doi.org/10.1186/1758-5996-4-32] [PMID: 22762794]
[54]
Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988; 37(9): 1163-7.
[http://dx.doi.org/10.2337/diab.37.9.1163] [PMID: 3044882]
[55]
Rossmeisl M, Rim JS, Koza RA, Kozak LP. Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity. Diabetes 2003; 52(8): 1958-66.
[http://dx.doi.org/10.2337/diabetes.52.8.1958] [PMID: 12882911]
[56]
Kim JK, Fillmore JJ, Chen Y, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci USA 2001; 98(13): 7522-7.
[http://dx.doi.org/10.1073/pnas.121164498] [PMID: 11390966]
[57]
Miyazaki M, Dobrzyn A, Man WC, et al. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 2004; 279(24): 25164-71.
[http://dx.doi.org/10.1074/jbc.M402781200] [PMID: 15066988]
[58]
Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): Two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie 2005; 87(1): 81-6.
[http://dx.doi.org/10.1016/j.biochi.2004.11.008] [PMID: 15733741]
[59]
Apfel R, Benbrook D, Lernhardt E, Ortiz MA, Salbert G, Pfahl M. A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol 1994; 14(10): 7025-35.
[PMID: 7935418]
[60]
Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 2006; 116(3): 607-14.
[http://dx.doi.org/10.1172/JCI27883] [PMID: 16511593]
[61]
Repa JJ, Liang G, Ou J, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ. Genes Dev 2000; 14(22): 2819-30.
[http://dx.doi.org/10.1101/gad.844900] [PMID: 11090130]
[62]
Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 2003; 17(6): 985-93.
[http://dx.doi.org/10.1210/me.2003-0061] [PMID: 12690094]
[63]
Schultz JR, Tu H, Luk A, et al. Role of LXRs in control of lipogenesis. Genes Dev 2000; 14(22): 2831-8.
[http://dx.doi.org/10.1101/gad.850400] [PMID: 11090131]
[64]
Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: Unravelling the mechanism. Lancet 2010; 375(9733): 2267-77.
[http://dx.doi.org/10.1016/S0140-6736(10)60408-4] [PMID: 20609972]
[65]
Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116(7): 1793-801.
[http://dx.doi.org/10.1172/JCI29069] [PMID: 16823477]
[66]
Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 2010; 314(1): 1-16.
[http://dx.doi.org/10.1016/j.mce.2009.07.031] [PMID: 19682539]
[67]
Brown MS, Goldstein JL. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA 1999; 96(20): 11041-8.
[http://dx.doi.org/10.1073/pnas.96.20.11041] [PMID: 10500120]
[68]
Knopp RH, Warth MR, Charles D, et al. Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes. Neonatology 1986; 50(6): 297-317.
[http://dx.doi.org/10.1159/000242614] [PMID: 3542067]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy