Suboptimal maternal nutrition during early-to-mid gestation in the sheep enhances pericardial adiposity in the near-term fetus
Shalini Ojha A , Michael E. Symonds A B and Helen Budge A
+ Author Affiliations
- Author Affiliations
A Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.
B Corresponding author. Email: michael.symonds@nottingham.ac.uk
Reproduction, Fertility and Development 27(8) 1205-1212 https://doi.org/10.1071/RD14007
Submitted: 9 January 2014 Accepted: 29 April 2014 Published: 23 June 2014
Abstract
Manipulation of the maternal diet at defined stages of gestation influences long-term health by inducing changes in fetal adipose tissue development, characterised as possessing brown and white adipocytes. We determined whether suboptimal maternal nutrition in early-to-mid gestation, followed by ad libitum feeding until term, increases adiposity in the pericardial depot of the sheep fetus. Pericardial adipose tissue was sampled from near-term (140 days) fetuses delivered to mothers fed either 100% (C) or 60% (i.e. nutrient restricted (NR)) of their total metabolisable requirements from 28 to 80 days gestation and then fed ad libitum. Adipose tissue mass, uncoupling protein (UCP) 1 and gene expression of brown and white adipogenic genes was measured. Total visceral and pericardial adiposity was increased in offspring born to NR mothers. The abundance of UCP1 was increased, together with those genes involved in brown (e.g. BMP7 and C/EBPβ) and white (e.g. BMP4 and C/EBPα) adipogenesis, whereas insulin receptor gene expression was downregulated. In conclusion, suboptimal maternal nutrition between early-to-mid gestation followed by ad libitum feeding enhances pericardial adiposity near to term. A combination of raised UCP1 and adipose tissue mass could improve survival following cold exposure at birth. In the longer term, this enhanced adipogenic potential could predispose to greater pericardial adiposity.
References
Agricutural and Food Research Council (AFRC) (1993). Agricutural and Food Research Council 1993 Technical Committee on Responses to Nutrients. (CAB International: London.)Barker, D. J. (1995). Fetal origins of coronary heart disease. BMJ 311, 171–174.
| Fetal origins of coronary heart disease.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2MzjvVSrtw%3D%3D&md5=4b4ea399e9df8c224a443f292f22efb4CAS | 7613432PubMed |
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J., and Sayers, E. W. (2011). GenBank. Nucleic Acids Res. 39, D32–D37.
| GenBank.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXivF2mt7s%3D&md5=09f68f9cb04dcda79bf09637ca94edc2CAS | 21071399PubMed |
Billon, N., and Dani, C. (2012). Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies. Stem Cell Rev. 8, 55–66.
| Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjtVCrtrg%3D&md5=9f26b018ba9dfa5681e65ded81927367CAS | 21365256PubMed |
Bispham, J., Gopalakrishnan, G. S., Dandrea, J., Wilson, V., Budge, H., Keisler, D. H., Broughton Pipkin, F., Stephenson, T., and Symonds, M. E. (2003). Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development. Endocrinology 144, 3575–3585.
| Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXlslGjt7g%3D&md5=6acf7af61bed9df7cc2e9cf230ca6e21CAS | 12865340PubMed |
Bronnikov, G., Bengtsson, T., Kramarova, L., Golozoubova, V., Cannon, B., and Nedergaard, J. (1999). beta1 to beta3 switch in control of cyclic adenosine monophosphate during brown adipocyte development explains distinct beta-adrenoceptor subtype mediation of proliferation and differentiation. Endocrinology 140, 4185–4197.
| 1:CAS:528:DyaK1MXlslSrtbg%3D&md5=57b389278634d4a50693568a47dd36b0CAS | 10465291PubMed |
Cannon, B., and Nedergaard, J. (2004). Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359.
| Brown adipose tissue: function and physiological significance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXotl2qsQ%3D%3D&md5=6e9659078361842dc1d38a1fdcc4a0f2CAS | 14715917PubMed |
Cantile, M., Procino, A., D’Armiento, M., Cindolo, L., and Cillo, C. (2003). HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis. J. Cell Physiol. 194, 225–236.
| HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXitlyktA%3D%3D&md5=8c94daf236e0acccfb35f1af15a6c47cCAS | 12494461PubMed |
Chan, L. L., Sebert, S. P., Hyatt, M. A., Stephenson, T., Budge, H., Symonds, M. E., and Gardner, D. S. (2009). Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1455–R1463.
| Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlvFantrg%3D&md5=021d4839612101f3414f5b929c2854d5CAS | 19244582PubMed |
DeFronzo, R. A., and Ferrannini, E. (1991). Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14, 173–194.
| Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M3ls1ymsw%3D%3D&md5=ba798404116338f3554b7d2e5e102e20CAS | 2044434PubMed |
Ding, J., Kritchevsky, S. B., Harris, T. B., Burke, G. L., Detrano, R. C., Szklo, M., Jeffrey Carr, J., Multi-Ethnic Study of Atherosclerosis (2008). The association of pericardial fat with calcified coronary plaque. Obesity (Silver Spring) 16, 1914–1919.
| The association of pericardial fat with calcified coronary plaque.Crossref | GoogleScholarGoogle Scholar | 18535554PubMed |
Fainberg, H. P., Sharkey, D., Sebert, S., Wilson, V., Pope, M., Budge, H., and Symonds, M. E. (2013). Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring. Reprod. Fertil. Dev. 25, 728–736.
| Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptVOqtbw%3D&md5=0d245a0272c4cb892e64e069f897b4c1CAS | 22951182PubMed |
Frühbeck, G., Sesma, P., and Burrell, M. A. (2009). PRDM16: the interconvertible adipo-myocyte switch. Trends Cell Biol. 19, 141–146.
| PRDM16: the interconvertible adipo-myocyte switch.Crossref | GoogleScholarGoogle Scholar | 19285866PubMed |
Gopalakrishnan, G. S., Gardner, D. S., Rhind, S. M., Rae, M. T., Kyle, C. E., Brooks, A. N., Walker, R. M., Ramsay, M. M., Keisler, D. H., Stephenson, T., and Symonds, M. E. (2004). Programming of adult cardiovascular function after early maternal undernutrition in sheep. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R12–R20.
| Programming of adult cardiovascular function after early maternal undernutrition in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmtVeksrc%3D&md5=69910ee23c8f330b7c34adec50def73aCAS | 14975924PubMed |
Harrington, T. A., Thomas, E. L., Frost, G., Modi, N., and Bell, J. D. (2004). Distribution of adipose tissue in the newborn. Pediatr. Res. 55, 437–441.
| Distribution of adipose tissue in the newborn.Crossref | GoogleScholarGoogle Scholar | 14681496PubMed |
Hyatt, M. A., Gardner, D. S., Sebert, S., Wilson, V., Davidson, N., Nigmatullina, Y., Chan, L. L., Budge, H., and Symonds, M. E. (2011). Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring. Reproduction 141, 119–126.
| Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXisVehs7Y%3D&md5=58e26e31cf814e81b01061962ad15a13CAS | 21045167PubMed |
Kajimura, S., Seale, P., Kubota, K., Lunsford, E., Frangioni, J. V., Gygi, S. P., and Spiegelman, B. M. (2009). Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 460, 1154–1158.
| Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXpt1WhtLs%3D&md5=40cfcb0fae237b56a4171be2ece3d5f2CAS | 19641492PubMed |
Kajimura, S., Seale, P., and Spiegelman, B. M. (2010). Transcriptional control of brown fat development. Cell Metab. 11, 257–262.
| Transcriptional control of brown fat development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlsVajtbs%3D&md5=80cbea40b484b351fedc14082e6feeceCAS | 20374957PubMed |
Liu, J., Fox, C. S., Hickson, D., Sarpong, D., Ekunwe, L., May, W. D., Hundley, G. W., Carr, J. J., and Taylor, H. A. (2010). Pericardial adipose tissue, atherosclerosis, and cardiovascular disease risk factors: the Jackson heart study. Diabetes Care 33, 1635–1639.
| Pericardial adipose tissue, atherosclerosis, and cardiovascular disease risk factors: the Jackson heart study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpslKgs70%3D&md5=82697de03a419246141f0f7ea1be22bcCAS | 20413524PubMed |
Merklin, R. J. (1974). Growth and distribution of human fetal brown fat. Anat. Rec. 178, 637–645.
| Growth and distribution of human fetal brown fat.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE2c7hs1Smsw%3D%3D&md5=3bb6e1ac5a975b6c1695f7562e20811eCAS | 4856126PubMed |
Ojha, S., Robinson, L., Symonds, M. E., and Budge, H. (2013a). Suboptimal maternal nutrition affects offspring health in adult life. Early Hum. Dev. 89, 909–913.
| Suboptimal maternal nutrition affects offspring health in adult life.Crossref | GoogleScholarGoogle Scholar | 24080391PubMed |
Ojha, S., Robinson, L., Yazdani, M., Symonds, M. E., and Budge, H. (2013b). Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation. Pediatr. Res. 74, 246–251.
| Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVWqtrfE&md5=fbbb8a3981a786f71f9abe7335b004ceCAS | 23788058PubMed |
Poissonnet, C. M., Burdi, A. R., and Bookstein, F. L. (1983). Growth and development of human adipose tissue during early gestation. Early Hum. Dev. 8, 1–11.
| Growth and development of human adipose tissue during early gestation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3s3gvFartQ%3D%3D&md5=86ff8ff309a5ffb7f963af8863e7685fCAS | 6851910PubMed |
Pope, M., Budge, H., and Symonds, M. E. (2014). The developmental transition of ovine adipose tissue through early life. Acta Physiol. (Oxf.) 210, 20–30.
| The developmental transition of ovine adipose tissue through early life.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvFalurzE&md5=1fd54ba8d0bfe3f0dd668c33bb7e1ae6CAS | 23351024PubMed |
Rosen, E. D., and Spiegelman, B. M. (2000). Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol. 16, 145–171.
| Molecular regulation of adipogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXpvFOm&md5=b38b013b27521e28ffe2eb38b88ac2cdCAS | 11031233PubMed |
Schmittgen, T. D., and Livak, K. J. (2008). Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 3, 1101–1108.
| Analyzing real-time PCR data by the comparative C(T) method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmvVemt7c%3D&md5=6defbbe8d2f1b6e9e7602068f826f4a9CAS | 18546601PubMed |
Scholzen, T., and Gerdes, J. (2000). The Ki-67 protein: from the known and the unknown. J. Cell Physiol. 182, 311–322.
| The Ki-67 protein: from the known and the unknown.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXot1Ggsg%3D%3D&md5=f594b642b95b37cb5711baaaae57120eCAS | 10653597PubMed |
Schulz, T. J., and Tseng, Y. H. (2009). Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism. Cytokine Growth Factor Rev. 20, 523–531.
| Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsV2msL%2FK&md5=3e253cf3815aa377361775edd7aa8696CAS | 19896888PubMed |
Seale, P., Kajimura, S., Yang, W., Chin, S., Rohas, L. M., Uldry, M., Tavernier, G., Langin, D., and Spiegelman, B. M. (2007). Transcriptional control of brown fat determination by PRDM16. Cell Metab. 6, 38–54.
| Transcriptional control of brown fat determination by PRDM16.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotlCitLo%3D&md5=05c2e8bb1ecdea8359cbc741b71f57feCAS | 17618855PubMed |
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. (1985). Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76–85.
| Measurement of protein using bicinchoninic acid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2MXlsFKksL0%3D&md5=55d1ad99a6d44df5696227b8ef558cd4CAS | 3843705PubMed |
Symonds, M. E., Bryant, M. J., Clarke, L., Darby, C. J., and Lomax, M. A. (1992). Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb. J. Physiol. 455, 487–502.
| 1:STN:280:DyaK3s7jt1OjsA%3D%3D&md5=eeb9ba564394355be5929d904f55e102CAS | 1484361PubMed |
Symonds, M. E., Mostyn, A., Pearce, S., Budge, H., and Stephenson, T. (2003). Endocrine and nutritional regulation of fetal adipose tissue development. J. Endocrinol. 179, 293–299.
| Endocrine and nutritional regulation of fetal adipose tissue development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhsF2htQ%3D%3D&md5=94d6365fba217628b17afc47fcde2fa7CAS | 14656200PubMed |
Symonds, M. E., Pope, M., Sharkey, D., and Budge, H. (2012). Adipose tissue and fetal programming. Diabetologia 55, 1597–1606.
| Adipose tissue and fetal programming.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xms1yqsbc%3D&md5=725d5e69898f0e9adfc9b6e1f1d3307cCAS | 22402988PubMed |
Taguchi, R., Takasu, J., Itani, Y., Yamamoto, R., Yokoyama, K., Watanabe, S., and Masuda, Y. (2001). Pericardial fat accumulation in men as a risk factor for coronary artery disease. Atherosclerosis 157, 203–209.
| Pericardial fat accumulation in men as a risk factor for coronary artery disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXksVGku7c%3D&md5=4e3cdc4a93f2788f39e906e80bea8ddaCAS | 11427222PubMed |
Tang, Q. Q., Otto, T. C., and Lane, M. D. (2004). Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc. Natl Acad. Sci. USA 101, 9607–9611.
| Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlvVahsLk%3D&md5=725801c4422fd768f53cb5cd80dba2deCAS | 15210946PubMed |
Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., Tran, T. T., Suzuki, R., Espinoza, D. O., Yamamoto, Y., Ahrens, M. J., Dudley, A. T., Norris, A. W., Kulkarni, R. N., and Kahn, C. R. (2008). New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000–1004.
| New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVWns7rP&md5=8c54284a83af33c67192f410e8991c8bCAS | 18719589PubMed |
Wellen, K. E., and Hotamisligil, G. S. (2005). Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111–1119.
| Inflammation, stress, and diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktFSksbY%3D&md5=ff9fea1a6bae0473ae3d2ab279f97a39CAS | 15864338PubMed |
