Citation: | MENG Yingying, ZHANG Jing, ZHANG Fenglin, AI Wei, ZHU Xiaotong, SHU Gang, WANG Lina, GAO Ping, JIANG Qingyan, WANG Songbo. Effect of high-fat diet on mammary gland development of pubertal mice and the molecular mechanism[J]. Journal of South China Agricultural University, 2017, 38(3): 9-14. DOI: 10.7671/j.issn.1001-411X.2017.03.002 |
To investigate the effect of high-fat diet (HFD) on mammary gland development of pubertal mice and explore the possible underlying mechanisms.
Twenty 4-week-old Kunming female mice were randomly divided into control group and HFD group. The trial lasted for four weeks. The body weight and feed intake were recorded weekly. At the end of the trial, mammary glands were collected and weighed. The morphology and number of ducts were observed by using whole-mount and HE staining. Western blot was used to analyze the expressions of insulin-like growth factor 1 (IGF-1), proliferation related signaling pathway proteins such as protein kinase B (Akt) and extracellular regulated protein kinases (ErK), as well as inflammation related signaling pathway proteins, including toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor kappa-B kinase (IKK) in the mammary glands.
The feed intake of the HFD group was significantly lower than that of control group(P < 0.05), There was no significant difference in energy intakes between two groups. The body weight gain of HFD group was significantly higher than that of control group (P < 0.05). In addition, HFD significantly increased mammary gland weight and the ratio of mammary gland weight to body weight (P < 0.01). The results of whole-mount and HE staining demonstrated that the mammary gland development of HFD group mice were markedly inhibited, with significantly decreased duct number, duct density and number of terminal end buds (P < 0.01). HFD significantly inhibited IGF-1 expression and the phosphorylation of Akt, Erk and IKK in mammary glands (P < 0.01 or 0.05), while significantly promoted TLR4 expression (P < 0.01) and JNK phosphorylation (P < 0.05).
HFD can suppress mammary gland development of pubertal mice, which might result from the inhibiton of proliferative signals and stimulation of inflammatory signals.
[1] |
FARMER C. Review: Mammary development in swine: Effects of hormonal status, nutrition and management[J]. Can J Anim Sci, 2013, 93(1): 1-7. doi: 10.4141/cjas2012-066
|
[2] |
MACIAS H, HINCK L. Mammary gland development[J]. Wiley Interdiscip Rev Dev Biol, 2012, 1(4): 533-557. doi: 10.1002/wdev.v1.4
|
[3] |
REZAEI R, WU Z, HOU Y, et al. Amino acids and mammary gland development: Nutritional implications for milk production and neonatal growth[J]. J Anim Sci Biotechno, 2016, 7(20). doi: 10. 1186/s40104-016-0078-8.
|
[4] |
FARMER C, PALIN M F, MARTEL-KENNES Y. Impact of diet deprivation and subsequent over-allowance during prepuberty: Part 1: Effects on growth performance, metabolite status, and mammary gland development in gilts[J]. J Anim Sci, 2012, 90(3): 863-871. doi: 10.2527/jas.2011-4131
|
[5] |
ZHAO Y, TAN Y S, AUPPERLEE M D, et al. Pubertal high fat diet: Effects on mammary cancer development[J]. Breast Cancer Res, 2013, 15(5): R100. doi: 10.1186/bcr3561
|
[6] |
李健, 李庆章.小鼠乳腺发育、泌乳和退化的组织形态学:Ⅰ:一般组织形态学变化[J].东北农业大学学报, 2007, 38(2): 196-201. http://www.cnki.com.cn/Article/CJFDTOTAL-DBDN200702012.htm
|
[7] |
李健, 李庆章.小鼠乳腺发育、泌乳和退化的组织形态学:Ⅱ:超微组织形态学变化和β-酪蛋白分泌[J].东北农业大学学报, 2007, 38(3): 374-379. http://www.cnki.com.cn/Article/CJFDTOTAL-DBDN200703021.htm
|
[8] |
MASUYAMA H, HIRAMATSU Y. Additive effects of maternal high fat diet during lactation on mouse offspring[J]. PLoS One, 2014, 9(3): e92805. doi: 10.1371/journal.pone.0092805
|
[9] |
MONTALES M T E, MELNYK S, SIMMEN R. Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem-like cells and increased maternal oxidative environment[J]. FASEB J, 2013, 27(Suppl 1): 235. 2. doi: 10.1007/978-1-4939-6386-7_13/fulltext.html
|
[10] |
KAMIKAWA A, ICHII O, YAMAJI D, et al. Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice[J]. Dev Dynam, 2009, 238(5): 1092-1099. doi: 10.1002/dvdy.v238:5
|
[11] |
MATSUBARA T, MITA A, MINAMI K, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue[J]. Cell Metab, 2012, 15(1): 38-50. doi: 10.1016/j.cmet.2011.12.002
|
[12] |
MCFARLANE M R, BROWN M S, GOLDSTEIN J L, et al. Induced ablation of ghrelin cells in adult mice does not decrease food intake, body weight, or response to high-fat diet[J]. Cell Metab, 2014, 20(1): 54-60. doi: 10.1016/j.cmet.2014.04.007
|
[13] |
OLSON L K, TAN Y, ZHAO Y, et al. Pubertal exposure to high fat diet causes mouse strain-dependent alterations in mammary gland development and estrogen responsiveness[J]. Int J Obes (Lond), 2010, 34(9): 1415-1426. doi: 10.1038/ijo.2010.51
|
[14] |
TIAN J, BERTON T R, SHIRLEY S H, et al. Developmental stage determines estrogen receptor alpha expression and non-genomic mechanisms that control IGF-1 signaling and mammary proliferation in mice[J]. J Clin Invest, 2012, 122(1): 192-204. doi: 10.1172/JCI42204
|
[15] |
BODEN G, SHE P, MOZZOLI M, et al. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver[J]. Diabetes, 2005, 54(12): 3458-3465. doi: 10.2337/diabetes.54.12.3458
|
[16] |
ZHANG X, ZHANG G, ZHANG H, et al. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity[J]. Cell, 2008, 135(1): 61-73. doi: 10.1016/j.cell.2008.07.043
|
[17] |
COWEN S, MCLAUGHLIN S L, HOBBS G et al. High-fat, high-calorie diet enhances mammary carcinogenesis and local inflammation in MMTV-PyMT mouse model of breast cancer[J]. Cancers, 2015, 7(3): 1125-1142. doi: 10.3390/cancers7030828
|
[18] |
SONG X, GUO M, WANG T et al. Geniposide inhibited lipopolysaccharide-induced apoptosis by modulating TLR4 and apoptosis-related factors in mouse mammary glands[J]. Life Sci, 2014, 119(1): 9-17. https://www.ncbi.nlm.nih.gov/pubmed/?term=Geniposide+Inhibited+Lipopolysaccharide-induced+Apoptosis+by+Modulating+TLR4+and+Apoptosis-related+Factors+in+Mouse+Mammary+Glands
|
[19] |
CELLURALE C, GIRNIUS N, JIANG F et al. Role of JNK in mammary gland development and breast cancer[J]. Cancer Res, 2012, 72(2): 472-481. doi: 10.1158/0008-5472.CAN-11-1628
|
[20] |
CAO Y, KARIN M. NF-kappaB in mammary gland development and breast cancer[J]. J Mammary Gland Biol Neoplasia, 2003, 8(2): 215-223. doi: 10.1023/A:1025905008934
|
1. |
杨帆,李优佳,SHAMEER K S,阎伟,吕宝乾,蒋方一丁,章雨璐,涂艳,齐可欣. 原产地与入侵地椰子织蛾遗传分化特征. 福建农林大学学报(自然科学版). 2021(02): 178-183 .
![]() |