Sex difference in the mouse BAT transcriptome reveals a role of progesterone

in Journal of Molecular Endocrinology
Authors:
Kasiphak Kaikaew Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Search for other papers by Kasiphak Kaikaew in
Current site
Google Scholar
PubMed Close
,
Aldo Grefhorst Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands

Search for other papers by Aldo Grefhorst in
Current site
Google Scholar
PubMed Close
,
Jacobie Steenbergen Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands

Search for other papers by Jacobie Steenbergen in
Current site
Google Scholar
PubMed Close
,
Sigrid M A Swagemakers Department of Pathology and Clinical Bioinformatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands

Search for other papers by Sigrid M A Swagemakers in
Current site
Google Scholar
PubMed Close
,
Anke McLuskey Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands

Search for other papers by Anke McLuskey in
Current site
Google Scholar
PubMed Close
, and
Jenny A Visser Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands

Search for other papers by Jenny A Visser in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to J A Visser: j.visser@erasmusmc.nl

*(K Kaikaew and A Grefhorst contributed equally to this work)

DOI:
https://doi.org/10.1530/JME-20-0210
Volume/Issue:
Volume 66: Issue 2
Article Type:
Research Article
Page Range:
97–113
Online Publication Date:
Feb 2021
Copyright:
© 2021 Society for Endocrinology 2021
Restricted access
Rent on DeepDyve

Sign up for journal news

Brown adipose tissue (BAT) is a metabolically active organ that exhibits sex-differential features, that is, being generally more abundant and active in females than in males. Although sex steroids, particularly estrogens, have been shown to regulate BAT thermogenic function, the underlying molecular mechanisms contributing to sexual dimorphism in basal BAT activity have not been elucidated. Therefore, we assessed the transcriptome of interscapular BAT of male and female C57BL/6J mice by RNA sequencing and identified 295 genes showing ≥2-fold differential expression (adjusted P < 0.05). In silico functional annotation clustering suggested an enrichment of genes encoding proteins involved in cell–cell contact, interaction, and adhesion. Ovariectomy reduced the expression of these genes in female BAT toward a male pattern whereas orchiectomy had marginal effects on the transcriptional pattern, indicating a prominent role of female gonadal hormones in this sex-differential expression pattern. Progesterone was identified as a possible upstream regulator of the sex-differentially expressed genes. Studying the direct effects of progesterone in vitro in primary adipocytes showed that progesterone significantly altered the transcription of several of the identified genes, possibly via the glucocorticoid receptor. In conclusion, this study reveals a sexually dimorphic transcription profile in murine BAT at general housing conditions and demonstrates a role for progesterone in the regulation of the interscapular BAT transcriptome.

Supplementary Materials

    • Supplementary Table 1 Selected genes from the significant functional annotation clusters and their functional description

Journal of Molecular Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 1401 67 3
PDF Downloads 1046 43 3

 

  • Collapse
  • Expand
Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
17
Article Type:
Research Article
Received Date:
05 Nov 2020
Accepted Date:
20 Nov 2020
Print Publication Date:
01 Feb 2021
Online Publication Date:
Feb 2021
Keywords:
brown adipose tissue; gonadal steroid hormones; primary cell culture; RNA sequencing; sex characteristics

  • Achari AE & Jain SK 2017 Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. International Journal of Molecular Sciences 18 E1321. (https://doi.org/10.3390/ijms18061321)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ali Khan A, Hansson J, Weber P, Foehr S, Krijgsveld J, Herzig S & Scheideler M 2018 Comparative secretome analyses of primary murine white and brown adipocytes reveal novel adipokines. Molecular and Cellular Proteomics 17 2358–2370. (https://doi.org/10.1074/mcp.RA118.000704)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Basu S, Cheriyamundath S & Ben-Ze’ev A 2018 Cell-cell adhesion: linking Wnt/beta-catenin signaling with partial EMT and stemness traits in tumorigenesis. F1000Research 7 7. (https://doi.org/10.12688/f1000research.15782.1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bora P & Majumdar AS 2017 Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Research and Therapy 8 145. (https://doi.org/10.1186/s13287-017-0598-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cannon B & Nedergaard J 2004 Brown adipose tissue: function and physiological significance. Physiological Reviews 84 277–359. (https://doi.org/10.1152/physrev.00015.2003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Choe SS, Huh JY, Hwang IJ, Kim JI & Kim JB 2016 Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Frontiers in Endocrinology 7 30. (https://doi.org/10.3389/fendo.2016.00030)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chouchani ET, Kazak L & Spiegelman BM 2019 New advances in adaptive thermogenesis: UCP1 and beyond. Cell Metabolism 29 27–37. (https://doi.org/10.1016/j.cmet.2018.11.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cianflone K, Xia Z & Chen LY 2003 Critical review of acylation-stimulating protein physiology in humans and rodents. Biochimica et Biophysica Acta 1609 127–143. (https://doi.org/10.1016/s0005-2736(0200686-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS & Scherer PE 2003 Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 52 268–276. (https://doi.org/10.2337/diabetes.52.2.268)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH & Doria A et al. 2009 Identification and importance of brown adipose tissue in adult humans. New England Journal of Medicine 360 1509–1517. (https://doi.org/10.1056/NEJMoa0810780)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M & Gingeras TR 2013 STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 15–21. (https://doi.org/10.1093/bioinformatics/bts635)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Engler JB, Kursawe N, Solano ME, Patas K, Wehrmann S, Heckmann N, Luhder F, Reichardt HM, Arck PC & Gold SM et al. 2017 Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy. PNAS 114 E181–E190. (https://doi.org/10.1073/pnas.1617115114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Feldmann HM, Golozoubova V, Cannon B & Nedergaard J 2009 UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metabolism 9 203–209. (https://doi.org/10.1016/j.cmet.2008.12.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH & Moradi-Lakeh M et al. 2017 Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine 377 13–27. (https://doi.org/10.1056/NEJMoa1614362)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Geer EB & Shen W 2009 Gender differences in insulin resistance, body composition, and energy balance. Gender Medicine 6 (Supplement 1) 60–75. (https://doi.org/10.1016/j.genm.2009.02.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Giles ED, Jackman MR, Johnson GC, Schedin PJ, Houser JL & MacLean PS 2010 Effect of the estrous cycle and surgical ovariectomy on energy balance, fuel utilization, and physical activity in lean and obese female rats. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 299 R1634–R 1642. (https://doi.org/10.1152/ajpregu.00219.2010)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gonzalez-Garcia I, Tena-Sempere M & Lopez M 2017 Estradiol regulation of brown adipose tissue thermogenesis. Advances in Experimental Medicine and Biology 1043 315–335. (https://doi.org/10.1007/978-3-319-70178-3_15)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Grefhorst A, van den Beukel JC, van Houten EL, Steenbergen J, Visser JA & Themmen AP 2015 Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice. Biology of Sex Differences 6 7. (https://doi.org/10.1186/s13293-015-0025-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gumbiner BM 1996 Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 84 345–357. (https://doi.org/10.1016/s0092-8674(0081279-9)

  • Hashimoto O, Noda T, Morita A, Morita M, Ohtsuki H, Sugiyama M & Funaba M 2016 Castration induced browning in subcutaneous white adipose tissue in male mice. Biochemical and Biophysical Research Communications 478 1746–1750. (https://doi.org/10.1016/j.bbrc.2016.09.017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang da W, Sherman BT & Lempicki RA 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4 44–57. (https://doi.org/10.1038/nprot.2008.211)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jacobs BR & Smith RG 1981 A comparison of progesterone and R5020 binding in endometrium, ovary, pituitary, and hypothalamus. Fertility and Sterility 35 438–441. (https://doi.org/10.1016/S0015-0282(1645440-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jeong JW, Lee KY, Kwak I, White LD, Hilsenbeck SG, Lydon JP & DeMayo FJ 2005 Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology 146 3490–3505. (https://doi.org/10.1210/en.2005-0016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jha RK, Titus S, Saxena D, Kumar PG & Laloraya M 2006 Profiling of E-cadherin, beta-catenin and Ca(2+) in embryo-uterine interactions at implantation. FEBS Letters 580 5653–5660. (https://doi.org/10.1016/j.febslet.2006.09.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Joo JI & Yun JW 2011 Gene expression profiling of adipose tissues in obesity susceptible and resistant rats under a high fat diet. Cellular Physiology and Biochemistry 27 327–340. (https://doi.org/10.1159/000327959)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kaikaew K, Steenbergen J, Themmen APN, Visser JA & Grefhorst A 2017 Sex difference in thermal preference of adult mice does not depend on presence of the gonads. Biology of Sex Differences 8 24. (https://doi.org/10.1186/s13293-017-0145-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kaikaew K, Steenbergen J, van Dijk TH, Grefhorst A & Visser JA 2019 Sex difference in corticosterone-induced insulin resistance in mice. Endocrinology 160 2367–2387. (https://doi.org/10.1210/en.2019-00194)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kramer A, Green J, Pollard Jr J & Tugendreich S 2014 Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30 523–530. (https://doi.org/10.1093/bioinformatics/btt703)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kroon J, Koorneef LL, van den Heuvel JK, Verzijl CRC, van de Velde NM, Mol IM, Sips HCM, Hunt H, Rensen PCN & Meijer OC 2018 Selective glucocorticoid receptor antagonist CORT125281 activates brown adipose tissue and alters lipid distribution in male mice. Endocrinology 159 535–546. (https://doi.org/10.1210/en.2017-00512)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lei K, Chen L, Georgiou EX, Sooranna SR, Khanjani S, Brosens JJ, Bennett PR & Johnson MR 2012 Progesterone acts via the nuclear glucocorticoid receptor to suppress IL-1beta-induced COX-2 expression in human term myometrial cells. PLoS ONE 7 e50167. (https://doi.org/10.1371/journal.pone.0050167)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liao Y, Smyth GK & Shi W 2014 featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30 923–930. (https://doi.org/10.1093/bioinformatics/btt656)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu X, Zheng Z, Zhu X, Meng M, Li L, Shen Y, Chi Q, Wang D, Zhang Z & Li C et al. 2013 Brown adipose tissue transplantation improves whole-body energy metabolism. Cell Research 23 851–854. (https://doi.org/10.1038/cr.2013.64)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu YF, Deng WB, Li SY, Yao MN, Liu J, Dou HT, Zhao ML, Yang ZM & Liang XH 2016 Progesterone induces the expression of lipocalin-2 through Akt-c-Myc pathway during mouse decidualization. FEBS Letters 590 2594–2602. (https://doi.org/10.1002/1873-3468.12304)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T, Kelly ME, Chatterjee Bhowmick D, Murano I & Cohen P et al. 2014 Adipsin is an adipokine that improves beta cell function in diabetes. Cell 158 41–53. (https://doi.org/10.1016/j.cell.2014.06.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Logue J, Walker JJ, Colhoun HM, Leese GP, Lindsay RS, McKnight JA, Morris AD, Pearson DW, Petrie JR & Philip S et al. 2011 Do men develop type 2 diabetes at lower body mass indices than women? Diabetologia 54 3003–3006. (https://doi.org/10.1007/s00125-011-2313-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P, Raciti GA, Beguinot F & Miele C 2019 Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. International Journal of Molecular Sciences 20 2358. (https://doi.org/10.3390/ijms20092358)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Love MI, Huber W & Anders S 2014 Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology 15 550. (https://doi.org/10.1186/s13059-014-0550-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Martin M 2011 Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.Journal 17 10–12. (https://doi.org/10.14806/ej.17.1.200)

  • Martinez de Morentin PB, Gonzalez-Garcia I, Martins L, Lage R, Fernandez-Mallo D, Martinez-Sanchez N, Ruiz-Pino F, Liu J, Morgan DA & Pinilla L et al. 2014 Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metabolism 20 41–53. (https://doi.org/10.1016/j.cmet.2014.03.031)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Maurer SF, Fromme T, Mocek S, Zimmermann A & Klingenspor M 2020 Uncoupling protein 1 and the capacity for nonshivering thermogenesis are components of the glucose homeostatic system. American Journal of Physiology: Endocrinology and Metabolism 318 E198–E215. (https://doi.org/10.1152/ajpendo.00121.2019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mauvais-Jarvis F 2015 Sex differences in metabolic homeostasis, diabetes, and obesity. Biology of Sex Differences 6 14. (https://doi.org/10.1186/s13293-015-0033-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mauvais-Jarvis F, Clegg DJ & Hevener AL 2013 The role of estrogens in control of energy balance and glucose homeostasis. Endocrine Reviews 34 309–338. (https://doi.org/10.1210/er.2012-1055)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McIlvride S, Mushtaq A, Papacleovoulou G, Hurling C, Steel J, Jansen E, Abu-Hayyeh S & Williamson C 2017 A progesterone-brown fat axis is involved in regulating fetal growth. Scientific Reports 7 10671. (https://doi.org/10.1038/s41598-017-10979-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Monjo M, Rodriguez AM, Palou A & Roca P 2003 Direct effects of testosterone, 17 beta-estradiol, and progesterone on adrenergic regulation in cultured brown adipocytes: potential mechanism for gender-dependent thermogenesis. Endocrinology 144 4923–4930. (https://doi.org/10.1210/en.2003-0537)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Moonen MPB, Nascimento EBM & van Marken Lichtenbelt WD 2019 Human brown adipose tissue: underestimated target in metabolic disease? Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids 1864 104–112. (https://doi.org/10.1016/j.bbalip.2018.05.012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Newell-Fugate AE 2017 The role of sex steroids in white adipose tissue adipocyte function. Reproduction 153 R133–R149. (https://doi.org/10.1530/REP-16-0417)

  • Nilsson ME, Vandenput L, Tivesten Å, Norlen AK, Lagerquist MK, Windahl SH, Borjesson AE, Farman HH, Poutanen M & Benrick A et al. 2015 Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry. Endocrinology 156 2492–2502. (https://doi.org/10.1210/en.2014-1890)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Palmer BF & Clegg DJ 2015 The sexual dimorphism of obesity. Molecular and Cellular Endocrinology 402 113–119. (https://doi.org/10.1016/j.mce.2014.11.029)

  • Panina YA, Yakimov AS, Komleva YK, Morgun AV, Lopatina OL, Malinovskaya NA, Shuvaev AN, Salmin VV, Taranushenko TE & Salmina AB 2018 Plasticity of adipose tissue-derived stem cells and regulation of angiogenesis. Frontiers in Physiology 9 1656. (https://doi.org/10.3389/fphys.2018.01656)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Perez-Perez R, Ortega-Delgado FJ, Garcia-Santos E, Lopez JA, Camafeita E, Ricart W, Fernandez-Real JM & Peral B 2009 Differential proteomics of omental and subcutaneous adipose tissue reflects their unalike biochemical and metabolic properties. Journal of Proteome Research 8 1682–1693. (https://doi.org/10.1021/pr800942k)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pope BD, Warren CR, Parker KK & Cowan CA 2016 Microenvironmental control of adipocyte fate and function. Trends in Cell Biology 26 745–755. (https://doi.org/10.1016/j.tcb.2016.05.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Poveda NE, Garces MF, Ruiz-Linares CE, Varon D, Valderrama S, Sanchez E, Castiblanco-Cortes A, Agudelo-Zapata Y, Sandoval-Alzate HF & Leal LG et al. 2016 Serum adipsin levels throughout normal pregnancy and preeclampsia. Scientific Reports 6 20073. (https://doi.org/10.1038/srep20073)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rodriguez AM, Monjo M, Roca P & Palou A 2002 Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cellular and Molecular Life Sciences 59 1714–1723. (https://doi.org/10.1007/pl00012499)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rodriguez-Cuenca S, Pujol E, Justo R, Frontera M, Oliver J, Gianotti M & Roca P 2002 Sex-dependent thermogenesis, differences in mitochondrial morphology and function, and adrenergic response in brown adipose tissue. Journal of Biological Chemistry 277 42958–42963. (https://doi.org/10.1074/jbc.M207229200)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rogers NH, Perfield 2nd JW, Strissel KJ, Obin MS & Greenberg AS 2009 Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 150 2161–2168. (https://doi.org/10.1210/en.2008-1405)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rudnicki M, Abdifarkosh G, Rezvan O, Nwadozi E, Roudier E & Haas TL 2018 Female mice have higher angiogenesis in perigonadal adipose tissue than males in response to high-fat diet. Frontiers in Physiology 9 1452. (https://doi.org/10.3389/fphys.2018.01452)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ruiz D, Padmanabhan V & Sargis RM 2020 Stress, sex, and sugar: glucocorticoids and sex-steroid crosstalk in the sex-specific misprogramming of metabolism. Journal of the Endocrine Society 4 bvaa087. (https://doi.org/10.1210/jendso/bvaa087)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Scioli MG, Bielli A, Gentile P, Mazzaglia D, Cervelli V & Orlandi A 2014 The biomolecular basis of adipogenic differentiation of adipose-derived stem cells. International Journal of Molecular Sciences 15 6517–6526. (https://doi.org/10.3390/ijms15046517)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Song NJ, Kim S, Jang BH, Chang SH, Yun UJ, Park KM, Waki H, Li DY, Tontonoz P & Park KW 2016 Small molecule-induced complement factor D (adipsin) promotes lipid accumulation and adipocyte differentiation. PLoS ONE 11 e0162228. (https://doi.org/10.1371/journal.pone.0162228)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Song A, Dai W, Jang MJ, Medrano L, Li Z, Zhao H, Shao M, Tan J, Li A & Ning T et al. 2020 Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. Journal of Clinical Investigation 130 247–257. (https://doi.org/10.1172/JCI129167)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Stelmanska E, Kmiec Z & Swierczynski J 2012 The gender- and fat depot-specific regulation of leptin, resistin and adiponectin genes expression by progesterone in rat. Journal of Steroid Biochemistry and Molecular Biology 132 160–167. (https://doi.org/10.1016/j.jsbmb.2012.05.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Stern JH, Rutkowski JM & Scherer PE 2016 Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metabolism 23 770–784. (https://doi.org/10.1016/j.cmet.2016.04.011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Townsend K & Tseng YH 2012 Brown adipose tissue: recent insights into development, metabolic function and therapeutic potential. Adipocyte 1 13–24. (https://doi.org/10.4161/adip.18951)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Villarroya J, Cereijo R, Gavalda-Navarro A, Peyrou M, Giralt M & Villarroya F 2019 New insights into the secretory functions of brown adipose tissue. Journal of Endocrinology 243 R19–R27. (https://doi.org/10.1530/JOE-19-0295)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Xu Y, Ma M, Ippolito GC, Schroeder Jr HW, Carroll MC & Volanakis JE 2001 Complement activation in factor D-deficient mice. PNAS 98 14577–14582. (https://doi.org/10.1073/pnas.261428398)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright EC & Stuelten C et al. 2011 Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling. Cell Metabolism 14 67–79. (https://doi.org/10.1016/j.cmet.2011.04.013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yao MW, Lim H, Schust DJ, Choe SE, Farago A, Ding Y, Michaud S, Church GM & Maas RL 2003 Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus. Molecular Endocrinology 17 610–627. (https://doi.org/10.1210/me.2002-0290)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yoshioka K, Yoshida T, Wakabayashi Y, Nishioka H & Kondo M 1988 Reduced brown adipose tissue thermogenesis of obese rats after ovariectomy. Endocrinologia Japonica 35 537–543. (https://doi.org/10.1507/endocrj1954.35.537)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zennaro MC, Le Menuet D, Viengchareun S, Walker F, Ricquier D & Lombes M 1998 Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. Journal of Clinical Investigation 101 1254–1260. (https://doi.org/10.1172/JCI1915)

    • PubMed
    • Search Google Scholar
    • Export Citation