Effect of Estradiol on Carbohydrate-Fat Metabolism and FGF21 System Activity in Female C57BL/6 Mice with Short-Term Consumption of the Cafeteria Diet

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Somente assinantes

Resumo

The cafeteria diet contributes to the development of obesity and metabolic syndrome, reduces insulin sensitivity and glucose tolerance. Hepatic hormone fibroblast growth factor 21 (FGF21) promotes adaptation to the consumption of sweet and fatty foods. Female mice are less sensitive to the damaging effects of the cafeteria diet than males, which may be due to the effect of estradiol on the activity of the FGF21 system: on the hepatic expression of the Fgf21 gene, on the blood level of hormone, or on the levels of receptors and coreceptors beta-clotho, which determine the sensitivity of tissues to FGF21. The purpose of this work was to verify this assumption. The effect of estradiol (10 mg/animal once every three days) was evaluated in ovariectomized female C57BL/6 mice who consumed a cafeteria diet (standard food, lard and cookies) for two weeks. Indicators of carbohydrate-fat metabolism, taste preferences, and activity of the FGF21 system were determined. Ovariectomy increased body weight and subcutaneous adipose tissue weight, fat intake, Pomc expression in the hypothalamus, decreased expression of estradiol receptors in the liver and cookie consumption. Estradiol did not have a significant effect on these parameters. In ovariectomized females with estradiol deficiency, blood cholesterol levels and liver expression of the glucose-6-phosphatase gene were lower than in sham operated females, and estradiol normalized these parameters. Ovariectomy lowered, and the administration of estradiol increased the level of coreceptor beta-clotho (Klb) mRNA in the liver and in the hypothalamus. These results suggest that at the initial stages of consumption of sweet and fatty foods, estradiol increases the sensitivity of the liver and hypothalamus to FGF21 and thereby enhances the contribution of the FGF21 system to the processes of adaptation to the cafeteria diet.

Texto integral

Acesso é fechado

Sobre autores

T. Jakovleva

Institute of Cytology and Genetics

Autor responsável pela correspondência
Email: tatyanajakovleva@yandex.ru
Rússia, Novosibirsk

A. Kazantseva

Institute of Cytology and Genetics

Email: tatyanajakovleva@yandex.ru
Rússia, Novosibirsk

K. Mamontova

Institute of Cytology and Genetics; Novosibirsk State University

Email: tatyanajakovleva@yandex.ru
Rússia, Novosibirsk; Novosibirsk

N. Bazhan

Institute of Cytology and Genetics; Novosibirsk State University

Email: tatyanajakovleva@yandex.ru
Rússia, Novosibirsk; Novosibirsk

Bibliografia

  1. Gadde KM, Martin CK, Berthoud HR, Heymsfield SB (2018) Obesity: Pathophysiology and Management. J Am Coll Cardiol 71(1): 69–84. https://doi.org/10.1016/j.jacc.2017.11.011
  2. Bruder-Nascimento T, Ekeledo OJ, Anderson R, Le HB, Belin de Chantemèle EJ (2017) Long Term High Fat Diet Treatment: An Appropriate Approach to Study the Sex-Specificity of the Autonomic and Cardiovascular Responses to Obesity in Mice. Front Physiol 8: 32. https://doi.org/10.3389/fphys.2017.00032
  3. Hwang LL, Wang CH, Li TL, Chang SD, Lin LC, Chen CP, Chen CT, Liang KC, Ho IK, Yang WS, Chiou LC (2010) Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity (Silver Spring) 18(3): 463–469. https://doi.org/10.1038/oby.2009.273
  4. Bazhan NM, Iakovleva TV, Dubinina AD, Makarova EN (2020) Impact of sex on the adaptation of adult mice to long consumption of sweet-fat diet. Vavilov Zhurn Genet Selekt 24(8): 844–852. https://doi.org/10.18699/VJ20.682
  5. Tramunt B, Smati S, Grandgeorge N, Lenfant F, Arnal JF, Montagner A, Gourdy P (2020) Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia 63(3): 453–461. https://doi.org/10.1007/s00125-019-05040-3
  6. Freire-Regatillo A, Fernández-Gómez MJ, Díaz F, Barrios V, Sánchez-Jabonero I, Frago LM, Argente J, García-Segura LM, Chowen JA (2020) Sex differences in the peripubertal response to a short-term, high-fat diet intake. J Neuroendocrinol 32(1): e12756. https://doi.org/10.1111/jne.12756
  7. Huang KP, Ronveaux CC, Knotts TA, Rutkowsky JR, Ramsey JJ, Raybould HE (2020) Sex differences in response to short-term high fat diet in mice. Physiol Behav 221: 112894. https://doi.org/10.1016/j.physbeh.2020.112894
  8. Nishimura T, Nakatake Y, Konishi M, Itoh N (2000) Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta 1492(1): 203. https://doi.org/10.1016/s0167-4781(00)00067-1
  9. Zhang P, Kuang H, He Y, Idiga SO, Li S, Chen Z, Yang Z, Cai X, Zhang K, Potthoff MJ, Xu Y, Lin JD (2018) NRG1-Fc improves metabolic health via dual hepatic and central action. JCI Insight 3(5): e98522. https://doi.org/10.1172/jci.insight.98522
  10. Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, Wang L, Goetz R, Mohammadi M, Kuroo M, Mangelsdorf DJ, Kliewer SA (2010) Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol 24(10): 2050. https://doi.org/10.1210/me.2010-0142
  11. Johnson CL, Weston JY, Chadi SA, Fazio EN, Huff MW, Kharitonenkov A, Köester A, Pin CL (2009) Fibroblast growth factor 21 reduces the severity of cerulein-induced pancreatitis in mice. Gastroenterology 137(5): 1795–1804. https://doi.org/10.1053/j.gastro.2009.07.064
  12. Patel V, Adya R, Chen J, Ramanjaneya M, Bari MF, Bhudia SK, Hillhouse EW, Tan BK, Randeva HS (2014) Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts. PLoS One 9(2): e87102. https://doi.org/10.1371/journal.pone.0087102
  13. Bazhan N, Jakovleva T, Balyibina N, Dubinina A, Denisova E, Feofanova N, Makarova E (2019) Sex Dimorphism in the Fgf21 Gene Expression in Liver and Adipose Tissues is Dependent on the Metabolic Condition. Online J Biol Sci 19(1): 28–36.
  14. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB (2005) FGF-21 as a novel metabolic regulator. J Clin Invest 115(6): 1627–1635. https://doi.org/10.1172/JCI23606
  15. Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M (2007) Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem 282(37): 26687. https://doi.org/10.1074/jbc.M704165200
  16. Suzuki M, Uehara Y, Motomura-Matsuzaka K, Oki J, Koyama Y, Kimura M, Asada M, Komi-Kuramochi A, Oka S, Imamura T (2008) betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c. Mol Endocrinol 22(4): 1006. https://doi.org/10.1210/me.2007-0313
  17. Bookout AL, de Groot MH, Owen BM, Lee S, Gautron L, Lawrence HL, Ding X, Elmquist JK, Takahashi JS, Mangelsdorf DJ, Kliewer SA (2013) FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med 19(9): 1147. https://doi.org/10.1038/nm.3249
  18. Jensen-Cody SO, Flippo KH, Claflin KE, Yavuz Y, Sapouckey SA, Walters GC, Usachev YM, Atasoy D, Gillum MP, Potthoff MJ (2020) FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake. Cell Metab 32(2): 273–286.e6. https://doi.org/10.1016/j.cmet.2020.06.008
  19. Yang ZH, Miyahara H, Takeo J, Katayama M (2012) 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 4(1): 32. https://doi.org/10.1186/1758-5996-4-32
  20. Lan T, Morgan DA, Rahmouni K, Sonoda J, Fu X, Burgess SC, Holland WL, Kliewer SA, Mangelsdorf DJ (2017) FGF19, FGF21, and an FGFR1/β-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia. Cell Metab 26(5): 709–718.e3. https://doi.org/10.1016/j.cmet.2017.09.005
  21. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE, Kharitonenkov A (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149(12): 6018–6027. https://doi.org/10.1210/en.2008-0816
  22. Larson KR, Chaffin AT, Goodson ML, Fang Y, Ryan KK (2019) Fibroblast Growth Factor-21 Controls Dietary Protein Intake in Male Mice. Endocrinology 160(5): 1069–1080. https://doi.org/10.1210/en.2018-01056
  23. Von Holstein-Rathlou S, Gillum MP (2019) Fibroblast growth factor 21: an endocrine inhibitor of sugar and alcohol appetite. J Physiol 597(14): 3539–3548. https://doi.org/10.1113/JP277117
  24. Hua L, Zhuo Y, Jiang D, Li J, Huang X, Zhu Y, Li Z, Yan L, Jin C, Jiang X, Che L, Fang Z, Lin Y, Xu S, Li J, Feng B, Wu D (2018) Identification of hepatic fibroblast growth factor 21 as a mediator in 17β-estradiol-induced white adipose tissue browning. FASEB J 32(10): 5602–5611. https://doi.org/10.1096/fj.201800240R
  25. Allard C, Bonnet F, Xu B, Coons L, Albarado D, Hill C, Fagherazzi G, Korach KS, Levin ER, Lefante J, Morrison C, Mauvais-Jarvis F (2019) Activation of hepatic estrogen receptor-α increases energy expenditure by stimulating the production of fibroblast growth factor 21 in female mice. Mol Metab 22: 62–70. https://doi.org/10.1016/j.molmet.2019.02.002
  26. Jakovleva TV, Kazantseva AY, Dubinina AD, Balybina NY, Baranov KO, Makarova EN, Bazhan NM (2022) Estradiol-dependent and independent effects of FGF21 in obese female mice. Vavilov Zhurn Genet Selekt 26(2): 159–168. https://doi.org/10.18699/VJGB-22-20
  27. Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, Fueger PT, Newgard CB, Makowski L (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity (Silver Spring, Md.) 19(6): 1109–1117. https://doi.org/10.1038/oby.2011.18
  28. Gao H, Bryzgalova G, Hedman E, Khan A, Efendic S, Gustafsson JA, Dahlman-Wright K (2006) Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol 20(6): 1287–1299. https://doi.org/10.1210/me.2006-0012
  29. Thammacharoen S, Geary N, Lutz TA, Ogawa S, Asarian L (2009) Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice. Brain Res 1268: 88–96. https://doi.org/10.1016/j.brainres.2009.02.067
  30. Kim JY, Jo KJ, Kim OS, Kim BJ, Kang DW, Lee KH, Baik HW, Han MS, Lee SK (2010) Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy. Life Sci 87(11-12): 358–366. https://doi.org/10.1016/j.lfs.2010.07.009
  31. Roesch SL, Styer AM, Wood GC, Kosak Z, Seiler J, Benotti P, Petrick AT, Gabrielsen J, Strodel WE, Gerhard GS, Still CD, Argyropoulos G (2015) Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes. PloS One 10(2): e0116928. https://doi.org/10.1371/journal.pone.0116928
  32. Bryzgalova G, Lundholm L, Portwood N, Gustafsson JA, Khan A, Efendic S, Dahlman-Wright K (2008) Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice. Am J Physiol Endocrinol Metab 295(4): E904–E912. https://doi.org/10.1152/ajpendo.90248.2008
  33. Fisher FM, Maratos-Flier E (2016) Understanding the Physiology of FGF21. Annu Rev Physiol 78: 223–241. https://doi.org/10.1146/annurev-physiol-021115-105339
  34. Makarova E, Kazantseva A, Dubinina A, et al. (2021) The Same Metabolic Response to FGF21 Administration in Male and Female Obese Mice Is Accompanied by Sex-Specific Changes in Adipose Tissue Gene Expression. Int J Mol Sci 22(19): 10561. https://doi.org/10.3390/ijms221910561
  35. Liu C, Schönke M, Zhou E, Li Z, Kooijman S, Boon MR, Larsson M, Wallenius K, Dekker N, Barlind L, Peng XR, Wang Y, Rensen PCN (2022) Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis. Cardiovasc Res 118(2): 489–502. https://doi.org/10.1093/cvr/cvab076
  36. Walf AA, Frye CA (2010) Estradiol reduces anxiety- and depression-like behavior of aged female mice. Physiol Behav 99(2): 169–174. https://doi.org/10.1016/j.physbeh.2009.09.017
  37. Dahir NS, Calder AN, McKinley BJ, Liu Y, Gilbertson TA (2021) Sex differences in fat taste responsiveness are modulated by estradiol. Am J Physiol Endocrinol Metab 320(3): E566– E580. https://doi.org/10.1152/ajpendo.00331.2020
  38. Yang TY, Liang NC (2018) Ovarian hormones mediate running-induced changes in high fat diet choice patterns in female rats. Horm Behav 100: 81–93. https://doi.org/10.1016/j.yhbeh.2018.02.010
  39. Sugaya A, Sugiyama T, Yanase S, Shen XX, Minoura H, Toyoda N (2000) Expression of glucose transporter 4 mRNA in adipose tissue and skeletal muscle of ovariectomized rats treated with sex steroid hormones. Life Sci 66(7): 641–648. https://doi.org/10.1016/s0024-3205(99)00636-0
  40. Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, Maratos-Flier E (2010) Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes 59(11): 2781– 2789. https://doi.org/10.2337/db10-0193
  41. Hale C, Chen MM, Stanislaus S, Chinookoswong N, Hager T, Wang M, Véniant MM, Xu J (2012) Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance. Endocrinology 153(1): 69–80. https://doi.org/10.1210/en.2010-1262
  42. Samms RJ, Cheng CC, Kharitonenkov A, Gimeno RE, Adams AC (2016) Overexpression of β-Klotho in Adipose Tissue Sensitizes Male Mice to Endogenous FGF21 and Provides Protection From Diet-Induced Obesity. Endocrinology 157(4): 1467–1480. https://doi.org/10.1210/en.2015-1722
  43. Santoso P, Nakata M, Shiizaki K, Boyang Z, Parmila K, Otgon-Uul Z, Hashimoto K, Satoh T, Mori M, Kuro-o M, Yada T (2017) Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states. Scient Rep 7: 45819. https://doi.org/10.1038/srep45819
  44. BonDurant LD, Potthoff MJ (2018) Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis. Annu Rev Nutr 38: 173–196. https://doi.org/10.1146/annurev-nutr-071816-064800
  45. Liang Q, Zhong L, Zhang J, Wang Y, Bornstein SR, Triggle CR, Ding H, Lam KS, Xu A (2014) FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting. Diabetes 63(12): 4064–4075. https://doi.org/10.2337/db14-0541
  46. Ornitz DM, Itoh N (2015) The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol 4(3): 215–266. https://doi.org/10.1002/wdev.176
  47. Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, Suino-Powell K, Xu HE, Gerard RD, Finck BN, Burgess SC, Mangelsdorf DJ, Kliewer SA (2011) FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. Cell Metab 13(6): 729–738. https://doi.org/10.1016/j.cmet.2011.03.019

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Fig. 1. Average daily energy consumption when kept on standard feed and cafeteria diet (a) and the proportion of energy consumed with each component of the diet during the experiment (b) in female mice of the C57Bl/6J line. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg / animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), t-test.

Baixar (121KB)
Metadados
3. Fig. 2. Dynamics of body weight (a) and body weight gain (b) during maintenance on the cafeteria diet in female mice of the C57Bl/6J line. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg/animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), t-test.

Baixar (121KB)
Metadados
4. 3. Body weight (a), liver mass index (b), brown (c), white subcutaneous (d) and visceral (e) fat in female mice of the C57Bl/6J line. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg/animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), t-test.

Baixar (110KB)
Metadados
5. 4. Blood levels of leptin (a), cholesterol (b), triglycerides (c), corticosterone (e), FGF21 (f), insulin (g) and glucose (h), triglycerides (d) and glycogen (i) in the liver of female C57Bl mice/6J. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg/animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), t-test.

Baixar (139KB)
Metadados
6. Fig. 5. mRNA levels of estradiol receptor genes (Gper, Esr1), leptin (Lepr), insulin (Insr) (a), neuropeptides (Agrp, Crh, Pomc) (b) and beta-clotho coreceptor (Klb) (c) in the hypothalamus of female C57Bl/6J mice. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg/animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), # – p < 0.05 compared to ovariectomized (OVX), t-test.

Baixar (112KB)
Metadados
7. 6. Levels of mRNA of estradiol receptor genes (Gper, Esr1), insulin signal transduction (Insr, Irs2) (a), FGF21 signal transduction (Fgf21, Klb) (b), transcription factor STAT3 (Stat3), protein phosphotyrosine phosphatase 1B (Ptpn1) and glucose-6-phosphatase (G6pc) (c) in the liver of female mice of the C57Bl/6J line. The females were falsely operated on or ovariectomized, consumed standard food, lard and biscuits (cafeteria diet), received orally once every three days at 16.00 – 16.30 estradiol (OVX+E2) at a dose of 10 mcg/animal or only solvent (sham and OVX). Estradiol was started a week before and administered during two weeks of maintenance on a cafeteria diet. * – p < 0.05 compared to falsely operated females (sham), t-test.

Baixar (119KB)
Metadados

Declaração de direitos autorais © Russian Academy of Sciences, 2024