Abstract
Numerous experimental studies have demonstrated that a series of remodeling processes occurred in the adipose tissue during the weaning, such as differentiation. Fibroblasts in the breast at weaning stage could re-differentiate into mature adipocytes. Many transcriptional factors were involved in these processes, especially the PPARγ, C/EBP, and SREBP1. There is cell apoptosis participating in the breast tissue degeneration and secretory epithelial cells loss during weaning. In addition, hormones, especially the estrogen and pituitary hormone, play a vital role in the whole reproductive processes. In this review, we mainly focus on the underlying regulated mechanisms of differentiation of adipose tissue and apoptosis of breast cell to provide a specific insight into the physiological changes during weaning.
Keywords: Adipose tissue, after weaning, mammary gland, adipose differentiation, C/EBP, ADD1/SREBP1.
Graphical Abstract
[1]
Smorlesi, A.; Frontini, A.; Giordano, A.; Cinti, S. The adipose organ: White-brown adipocyte plasticity and metabolic inflammation. Obes. Rev., 2012, 13, 83-96.
[2]
Bevers, M.M.; Willemse, A.H.; Kruip, T.A. Plasma prolactin levels in the sow during lactation and the postweaning period as measured by radioimmunoassay. Biol. Reprod., 1978, 19, 628-634.
[3]
Rosen, E.D.; Spiegelman, B.M. What we talk about when we talk about fat. Cell, 2014, 156, 20-44.
[4]
Cinti, S. Reversible physiological transdifferentiation in the adipose organ. Proc. Nutr. Soc., 2009, 68, 340-349.
[5]
Ouchi, N.; Parker, J.L.; Lugus, J.J.; Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol., 2011, 11, 85-97.
[6]
Giordano, A.; Smorlesi, A.; Frontini, A.; Barbatelli, G.; Cinti, S. White, brown and pink adipocytes: The extraordinary plasticity of the adipose organ. Eur. J. Endocrinol., 2014, 170, R159-R171.
[7]
Elias, J.J.; Pitelka, D.R.; Armstrong, R.C. Changes in fat cell morphology during lactation in the mouse. Anat. Rec., 1973, 177, 533-547.
[8]
Stingl, J.; Eaves, C.J.; Zandieh, I.; Emerman, J.T. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res. Treat., 2001, 67, 93-109.
[9]
Raouf, A.; Zhao, Y.; To, K.; Stingl, J.; Delaney, A.; Barbara, M.; Iscove, N.; Jones, S.; McKinney, S.; Emerman, J.; Aparicio, S.; Marra, M.; Eaves, C. Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell, 2008, 3, 109-118.
[10]
Darcy, K.M.; Zangani, D.; Shea-Eaton, W.; Shoemaker, S.F.; Lee, P.P.; Mead, L.H.; Mudipalli, A.; Megan, R.; Ip, M.M. Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells. In Vitro Cell. Dev. Biol. Anim., 2000, 36, 578-592.
[11]
Neville, M.C.; Medina, D.; Monks, J.; Hovey, R.C. The mammary fat pad. J. Mammary Gland Biol. Neoplasia, 1998, 3, 109-116.
[12]
Wiseman, B.S.; Werb, Z. Stromal effects on mammary gland development and breast cancer. Science, 2002, 296, 1046-1049.
[13]
Levine, J.F.; Stockdale, F.E. 3t3-l1 adipocytes promote the growth of mammary epithelium. Exp. Cell Res., 1984, 151, 112-122.
[14]
Levine, J.F.; Stockdale, F.E. Cell-cell interactions promote mammary epithelial cell differentiation. J. Cell Biol., 1985, 100, 1415-1422.
[15]
Wiens, D.; Park, C.S.; Stockdale, F.E. Milk protein expression and ductal morphogenesis in the mammary gland in vitro: Hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction. Dev. Biol., 1987, 120, 245-258.
[16]
Zangani, D.; Darcy, K.M.; Shoemaker, S.; Ip, M.M. Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells. Exp. Cell Res., 1999, 247, 399-409.
[17]
Hovey, R.C.; Aimo, L. Diverse and active roles for adipocytes during mammary gland growth and function. J. Mammary Gland Biol. Neoplasia, 2010, 15, 279-290.
[18]
Li, M.; Liu, X.; Robinson, G.; Bar-Peled, U.; Wagner, K.U.; Young, W.S.; Hennighausen, L.; Furth, P.A. Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc. Natl. Acad. Sci. USA, 1997, 94, 3425-3430.
[19]
Kordon, E.C.; Smith, G.H. An entire functional mammary gland may comprise the progeny from a single cell. Development, 1998, 125, 1921-1930.
[20]
Hens, J.R.; Wysolmerski, J.J. Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res., 2005, 7, 220-224.
[21]
Ferguson, D.J.; Anderson, T.J. A morphological study of the changes which occur during pregnancy in the human breast. Virchows Arch. A Pathol. Anat. Histopathol., 1983, 401, 163-175.
[22]
Joshi, K.; Ellis, J.T.; Hughes, C.M.; Monaghan, P.; Neville, A.M. Cellular proliferation in the rat mammary gland during pregnancy and lactation. Lab. Invest., 1986, 54, 52-61.
[23]
Steingrimsdottir, L.; Brasel, J.A.; Greenwood, M.R. Diet, pregnancy, and lactation: Effects on adipose tissue, lipoprotein lipase, and fat cell size. Metabolism, 1980, 29, 837-841.
[24]
Visvader, J.E. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev., 2009, 23, 2563-2577.
[25]
Rillema, J.A. Development of the mammary gland and lactation. Trends Endocrinol. Metab., 1994, 5, 149-154.
[26]
Lund, L.R.; Romer, J.; Thomasset, N.; Solberg, H.; Pyke, C.; Bissell, M.J.; Dano, K.; Werb, Z. Two distinct phases of apoptosis in mammary gland involution: Proteinase-independent and -dependent pathways. Development, 1996, 122, 181-193.
[27]
Monks, J.; Rosner, D.; Geske, F.J.; Lehman, L.; Hanson, L.; Neville, M.C.; Fadok, V.A. Epithelial cells as phagocytes: Apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ., 2005, 12, 107-114.
[28]
Wang, D.; Cai, C.; Dong, X.; Yu, Q.C.; Zhang, X.O.; Yang, L.; Zeng, Y.A. Identification of multipotent mammary stem cells by protein c receptor expression. Nature, 2015, 517, 81-84.
[30]
Watson, C.J.; Kreuzaler, P.A. Remodeling mechanisms of the mammary gland during involution. Int. J. Dev. Biol., 2011, 55, 757-762.
[31]
Rudolph, M.C.; McManaman, J.L.; Hunter, L.; Phang, T.; Neville, M.C. Functional development of the mammary gland: Use of expression profiling and trajectory clustering to reveal changes in gene expression during pregnancy, lactation, and involution. J. Mammary Gland Biol. Neoplasia, 2003, 8, 287-307.
[32]
Wang, Q.A.; Song, A.Y.; Chen, W.Z.; Schwalie, P.C.; Zhang, F.; Vishvanath, L.; Jiang, L.; Ye, R.S.; Shao, M.L.; Tao, C.; Gupta, R.K.; Deplancke, B.; Scherer, P.E. Reversible de-differentiation of mature white adipocytes into preadipocyte-like precursors during lactation. Cell Metab., 2018, 28, 282.
[33]
Morroni, M.; Giordano, A.; Zingaretti, M.C.; Boiani, R.; De Matteis, R.; Kahn, B.B.; Nisoli, E.; Tonello, C.; Pisoschi, C.; Luchetti, M.M.; Marelli, M.; Cinti, S. Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland. Proc. Natl. Acad. Sci. USA, 2004, 101, 16801-16806.
[34]
Monden, M.; Koyama, H.; Otsuka, Y.; Morioka, T.; Mori, K.; Shoji, T.; Mima, Y.; Motoyama, K.; Fukumoto, S.; Shioi, A.; Emoto, M.; Yamamoto, Y.; Yamamoto, H.; Nishizawa, Y.; Kurajoh, M.; Yamamoto, T.; Inaba, M. Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: Involvement of toll-like receptor 2. Diabetes, 2013, 62, 478-489.
[35]
Cheng, H.S.; Ton, S.H.; Phang, S.C.W.; Tan, J.B.L.; Abdul Kadir, K. Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome. J. Adv. Res., 2017, 8, 743-752.
[36]
Symonds, M.E.; Sebert, S.P.; Hyatt, M.A.; Budge, H. Nutritional programming of the metabolic syndrome. Nat. Rev. Endocrinol., 2009, 5, 604-610.
[37]
Tontonoz, P.; Graves, R.A.; Budavari, A.I.; Erdjumentbromage, H.; Lui, M.; Hu, E.; Tempst, P.; Spiegelman, B.M. Adipocyte-specific transcription factor-arf6 is a heterodimeric complex of 2 nuclear hormone receptors, ppar-gamma and rxr-alpha. Nucleic Acids Res., 1994, 22, 5628-5634.
[38]
VidalPuig A.J.; Considine, R.V.; JimenezLinan, M.; Werman, A.; Pories, W.J.; Caro, J.F.; Flier, J.S. Peroxisome proliferator-activated receptor gene expression in human tissues - effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest., 1997, 99, 2416-2422.
[39]
Hsu, S.F.; Chao, C.M.; Huang, W.T.; Lin, M.T.; Cheng, B.C. Attenuating heat-induced cellular autophagy, apoptosis and damage in h9c2 cardiomyocytes by pre-inducing hsp70 with heat shock preconditioning. Int. J. Hyperthermia, 2013, 29, 239-247.
[40]
Ma, X.; Ren, X.; Han, P.; Hu, S.; Wang, J.; Yin, J. SiRNA against Fabp5 induces 3T3-L1 cells apoptosis during adipocytic induction. Mol. Biol. Rep., 2010, 37(8), 4003-4011.
[41]
Xing, B.; Wang, L.; Li, Q.; Cao, Y.; Dong, X.; Liang, J.; Wu, X. Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice. J. Physiol. Biochem., 2015, 71, 649-658.
[42]
Sferruzzi-Perri, A.N.; Vaughan, O.R.; Haro, M.; Cooper, W.N.; Musial, B.; Charalambous, M.; Pestana, D.; Ayyar, S.; Ferguson-Smith, A.C.; Burton, G.J.; Constancia, M.; Fowden, A.L. An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J., 2013, 27, 3928-3937.
[43]
Ma, X.; Ding, W.; Wang, J.; Wu, G.; Zhang, H.; Yin, J.; Zhou, L.; Li, D. LOC66273 isoform 2, a novel protein highly expressed in white adipose tissue, induces adipogenesis in 3T3-L1 cells. J. Nutr., 2012, 142(3), 448-455.
[44]
Wu, Z.; Bucher, N.L.; Farmer, S.R. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3t3 fibroblasts into adipocytes is mediated by c/ebpbeta, c/ebpdelta, and glucocorticoids. Mol. Cell. Biol., 1996, 16, 4128-4136.
[45]
Darlington, G.J.; Ross, S.E.; MacDougald, O.A. The role of c/ebp genes in adipocyte differentiation. J. Biol. Chem., 1998, 273, 30057-30060.
[46]
Yeh, W.C.; Cao, Z.; Classon, M.; McKnight, S.L. Cascade regulation of terminal adipocyte differentiation by three members of the c/ebp family of leucine zipper proteins. Genes Dev., 1995, 9, 168-181.
[47]
Wu, Z.; Xie, Y.; Bucher, N.L.; Farmer, S.R. Conditional ectopic expression of c/ebp beta in nih-3t3 cells induces ppar gamma and stimulates adipogenesis. Genes Dev., 1995, 9, 2350-2363.
[48]
Hwang, C.S.; Mandrup, S.; MacDougald, O.A.; Geiman, D.E.; Lane, M.D. Transcriptional activation of the mouse obese (ob) gene by ccaat/enhancer binding protein alpha. Proc. Natl. Acad. Sci. USA, 1996, 93, 873-877.
[49]
MacDougald, O.A.; Lane, M.D. Transcriptional regulation of gene expression during adipocyte differentiation. Annu. Rev. Biochem., 1995, 64, 345-373.
[50]
Lin, F.T.; Lane, M.D. Antisense ccaat/enhancer-binding protein rna suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3t3-l1 preadipocytes. Genes Dev., 1992, 6, 533-544.
[51]
Lin, F.T.; Lane, M.D. Ccaat/enhancer binding protein alpha is sufficient to initiate the 3t3-l1 adipocyte differentiation program. Proc. Natl. Acad. Sci. USA, 1994, 91, 8757-8761.
[52]
Harris, P.K.W.; Kletzien, R.F. Localization of a pioglitazone response element in the adipocyte fatty-acid-binding protein gene. Mol. Pharmacol., 1994, 45, 439-445.
[53]
Wu, Z.; Rosen, E.D.; Brun, R.; Hauser, S.; Adelmant, G.; Troy, A.E.; McKeon, C.; Darlington, G.J.; Spiegelman, B.M. Cross-regulation of c/ebp alpha and ppar gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol. Cell, 1999, 3, 151-158.
[54]
Wellings, S.R.; Deome, K.B. Electron microscopy of milk secretion in the mammary gland of the c3h/crgl mouse. III. Cytomorphology of the involuting gland. J. Natl. Cancer Inst., 1963, 30, 241-267.
[55]
Strange, R.; Li, F.; Saurer, S.; Burkhardt, A.; Friis, R.R. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development, 1992, 115, 49-58.
[56]
Quarrie, L.H.; Addey, C.V.; Wilde, C.J. Programmed cell death during mammary tissue involution induced by weaning, litter removal, and milk stasis. J. Cell. Physiol., 1996, 168, 559-569.
[57]
Martinez-Hernandez, A.; Fink, L.M.; Pierce, G.B. Removal ofbasement membrane in the involuting breast. Lab. Invest., 1976, 34, 455-462.
[58]
Warburton, M.J.; Mitchell, D.; Ormerod, E.J.; Rudland, P. Distribution of myoepithelial cells and basement membrane proteins in the resting, pregnant, lactating, and involuting rat mammary gland. J. Histochem. Cytochem., 1982, 30, 667-676.
[59]
Compton, M.M.; Cidlowski, J.A. Identification of a glucocorticoid-induced nuclease in thymocytes. A potential “lysis gene” product. J. Biol. Chem., 1987, 262, 8288-8292.
[60]
Cohen, J.J.; Duke, R.C. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J. Immunol., 1984, 132, 38-42.
[61]
Wyllie, A.H.; Kerr, J.F.; Currie, A.R. Cell death: The significance of apoptosis. Int. Rev. Cytol., 1980, 68, 251-306.
[62]
Wyllie, A.H.; Morris, R.G.; Smith, A.L.; Dunlop, D. Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis. J. Pathol., 1984, 142, 67-77.
[64]
Feng, Z.; Zhang, H.; Levine, A.J.; Jin, S. The coordinate regulation of the p53 and mtor pathways in cells. Proc. Natl. Acad. Sci. USA, 2005, 102, 8204-8209.
[65]
Karuman, P.; Gozani, O.; Odze, R.D.; Zhou, X.C.; Zhu, H.; Shaw, R.; Brien, T.P.; Bozzuto, C.D.; Ooi, D.; Cantley, L.C.; Yuan, J. The peutz-jegher gene product lkb1 is a mediator of p53-dependent cell death. Mol. Cell, 2001, 7, 1307-1319.
[66]
Stambolic, V.; MacPherson, D.; Sas, D.; Lin, Y.; Snow, B.; Jang, Y.; Benchimol, S.; Mak, T.W. Regulation of pten transcription by p53. Mol. Cell, 2001, 8, 317-325.
[67]
Lyons, W.R.; Li, C.H.; Johnson, R.E. The hormonal control of mammary growth and lactation. Recent Prog. Horm. Res., 1958, 14, 219-248. discussion 248-254.
[68]
Bachman, K.C.; Hayen, M.J.; Morse, D.; Wilcox, C.J. Effect of pregnancy, milk yield, and somatic cell count on bovine milk fat hydrolysis. J. Dairy Sci., 1988, 71, 925-931.
[70]
Soemarwoto, I.N.; Bern, H.A. The effect of hormones on the vascular pattern of the mouse mammary gland. Am. J. Anat., 1958, 103, 403-435.
[71]
Matsumoto, M.; Nishinakagawa, H.; Kurohmaru, M.; Hayashi, Y.; Otsuka, J. Effects of estrogen and progesterone on the development of the mammary gland and the associated blood vessels in ovariectomized mice. J. Vet. Med. Sci., 1992, 54, 1117-1124.
[72]
Stewart, W.C.; Baugh, J.E., Jr; Floyd, Z.E.; Stephens, J.M. Stat 5 activators can replace the requirement of fbs in the adipogenesis of 3t3-l1 cells. Biochem. Biophys. Res. Commun., 2004, 324, 355-359.
[73]
Nanbu-Wakao, R.; Fujitani, Y.; Masuho, Y.; Muramatu, M.; Wakao, H. Prolactin enhances ccaat enhancer-binding protein-beta (c/ebp beta) and peroxisome proliferator-activated receptor gamma (ppar gamma) messenger rna expression and stimulates adipogenic conversion of nih-3t3 cells. Mol. Endocrinol., 2000, 14, 307-316.
[74]
Flint, D.J.; Binart, N.; Kopchick, J.; Kelly, P. Effects of growth hormone and prolactin on adipose tissue development and function. Pituitary, 2003, 6, 97-102.
[75]
Darcy, K.M.; Zangani, D.; Shea-Eaton, W.; Shoemaker, S.F.; Lee, P.P.H.; Mead, L.H.; Mudipalli, A.; Megan, R.; Ip, M.M. Mammary
fibroblasts stimulate growth, alveolar morphogenesis, and functional
differentiation of normal rat mammary epithelial cells. In Vitro
Cell Dev-An , 2000; 36, pp. 578-592.
Related Journals
Protein & Peptide Letters
Related Books
Frontiers in Protein and Peptide Sciences
Article Metrics
32
4
1
1