{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:48:26Z","timestamp":1790671706177,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Genentech Fellowship grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. We investigated the impact of GH on cachexia brought on by CKD. CKD was induced by 5\/6 nephrectomy in c57BL\/6J mice. After receiving GH (10 mg\/kg\/day) or saline treatment for six weeks, CKD mice were compared to sham-operated controls. GH normalized metabolic rate, increased food intake and weight growth, and improved in vivo muscular function (rotarod and grip strength) in CKD mice. GH decreased uncoupling proteins (UCP)s and increased muscle and adipose tissue ATP content in CKD mice. GH decreased lipolysis of adipose tissue by attenuating expression and protein content of adipose triglyceride lipase and protein content of phosphorylated hormone-sensitive lipase in CKD mice. GH reversed the increased expression of beige adipocyte markers (UCP-1, CD137, Tmem26, Tbx1, Prdm16, Pgc1\u03b1, and Cidea) and molecules implicated in adipose tissue browning (Cox2\/Pgf2\u03b1, Tlr2, Myd88, and Traf6) in CKD mice. Additionally, GH normalized the molecular markers of processes connected to muscle wasting in CKD, such as myogenesis and muscle regeneration. By using RNAseq, we previously determined the top 12 skeletal muscle genes differentially expressed between mice with CKD and control animals. These 12 genes\u2019 aberrant expression has been linked to increased muscle thermogenesis, fibrosis, and poor muscle and neuron regeneration. In this study, we demonstrated that GH restored 7 of the top 12 differentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.<\/jats:p>","DOI":"10.3390\/ijms232315310","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Growth Hormone Improves Adipose Tissue Browning and Muscle Wasting in Mice with Chronic Kidney Disease-Associated Cachexia"],"prefix":"10.3390","volume":"23","author":[{"given":"Robert H.","family":"Mak","sequence":"first","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujana","family":"Gunta","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"},{"name":"Pediatric Services, Vista Community Clinic, Vista, CA 92084, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"},{"name":"Department of Pediatrics, Health Sciences Postgraduate Program, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte 30310-100, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai W.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s13539-011-0019-5","article-title":"Wasting in Chronic Kidney Disease","volume":"2","author":"Mak","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/jcsm.12421","article-title":"Kidney Cachexia or Protein-Energy Wasting in CKD: Facts and Numbers","volume":"10","author":"Koppe","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/jcsm.12839","article-title":"Effects of Hormonal Changes on Sarcopenia in Chronic Kidney Disease: Where are we now and what can we do?","volume":"12","author":"Gungor","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.semnephrol.2021.03.009","article-title":"The Role of Growth Hormone in Chronic Kidney Disease","volume":"41","author":"Oliveria","year":"2021","journal-title":"Semin. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"942030","DOI":"10.1155\/2013\/942030","article-title":"Effects of Growth Hormone Administration on Muscle Strength in Men over 50 Years Old","volume":"2013","author":"Tavares","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1172\/JCI119139","article-title":"Effects of Recombinant Human Growth Hormone on Muscle Protein Turnover in Malnourished Hemodialysis Patients","volume":"99","author":"Gabribotto","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_7","first-page":"99","article-title":"Influence of Growth hormone on Whole Body and Regional Soft Tissue Composition in Adult Patients on Hemodialysis. A Double-Blind, Randomized, Placebo-Controlled Study","volume":"53","author":"Hansen","year":"2000","journal-title":"Clin. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1681\/ASN.2006111207","article-title":"Growth Hormone Treatment during Hemodialysis in a Randomized Trial Improves Nutrition, Quality of Life, and Cardiovascular Risk","volume":"18","author":"Lange","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/ki.2009.480","article-title":"A Super-Agonist of Growth Hormone-Releasing Hormone Causes Rapid Improvement of Nutritional Status in Patients with Chronic Kidney Disease","volume":"77","author":"Nienczyk","year":"2010","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1177\/0363546520920591","article-title":"The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial","volume":"48","author":"Mendias","year":"2020","journal-title":"Am. J. Sports Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10028","DOI":"10.1038\/s41598-019-46428-w","article-title":"Changes in DXA-Derived Lean Mass and MRI-Derived Cross-Sectional Area of the Thigh are Modestly Associated","volume":"9","author":"Tavoian","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.21037\/qims.2020.03.05","article-title":"Muscle Mass Assessment in Renal Disease: The Role of Imaging Techniques","volume":"10","author":"Sabatino","year":"2020","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1681\/ASN.2013040432","article-title":"A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice","volume":"25","author":"Cheung","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/sj.ki.5001532","article-title":"Work-Induced Changes in Skeletal Muscle IGF-1 and Myostatin Gene Expression in Uremia","volume":"70","author":"Sun","year":"2006","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1172\/JCI11895","article-title":"Impaired JAK-STAT Signal Transduction Contributes to Growth Hormone Resistance in Chronic Uremia","volume":"108","author":"Schaefer","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fendo.2016.00030","article-title":"Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders","volume":"7","author":"Choe","year":"2016","journal-title":"Front. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature13528","article-title":"Tumor-Derived PTHrP Triggers Adipose Tissue Browning and Cancer Cachexia","volume":"513","author":"Kir","year":"2014","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cmet.2015.11.003","article-title":"PTH\/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer","volume":"23","author":"Kir","year":"2016","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Berryman, D.E., and List, E.O. (2017). Growth Hormone\u2019s Effect on Adipose Tissue: Quality versus Quantity. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081621"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41574-019-0280-9","article-title":"The Effects of Growth Hormone on Adipose Tissue: Old Observations, New Mechanisms","volume":"16","author":"Kopchick","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"886","DOI":"10.4161\/15384047.2014.987075","article-title":"Adipose tissue lipolysis and energy metabolism in early cancer cachexia mice","volume":"16","author":"Kliewer","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.1186034","article-title":"Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de Novo Recruitment of Brown Adipocytes","volume":"328","author":"Vegiopoulos","year":"2010","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14175","DOI":"10.1038\/s41598-020-70190-z","article-title":"Vitamin D Ameliorates Adipose Browning in Chronic Kidney Disease Cachexia","volume":"10","author":"Cheung","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/ajcn\/82.6.1235","article-title":"Recombinant Human Growth Hormone Improves Muscle Amino Acid Uptake and Whole-Body Protein Metabolism in Chronic Hemodialysis Patients","volume":"82","author":"Pupim","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1469-7793.2000.00003.x","article-title":"Mitochondrial uncoupling proteins: From mitochondria to the regulation of energy balance","volume":"529","author":"Ricquier","year":"2000","journal-title":"J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Demine, S., Renard, P., and Arnould, T. (2019). Mitochondrial uncoupling: A key controller of biological processes in physiology and diseases. Cells, 8.","DOI":"10.3390\/cells8080795"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E512","DOI":"10.1152\/ajpendo.00446.2002","article-title":"Expression of uncoupling protein is upregulated in skeletal muscle during sepsis","volume":"285","author":"Sun","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3389\/fphys.2019.00470","article-title":"Important trends in UCP3 investigation","volume":"10","author":"Pohl","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5172","DOI":"10.1016\/j.febslet.2006.08.066","article-title":"UCP3 in muscle wasting, a role in modulating lipotoxicity?","volume":"580","author":"Minnaard","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2014.06.011","article-title":"A switch from white to brown fat increased energy expenditure in cancer-associated cachexia","volume":"20","author":"Petruzzelli","year":"2014","journal-title":"Cell Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/nm.4171","article-title":"An AMP-activated protein kinase\u2013stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice","volume":"22","author":"Rohm","year":"2016","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/jcsm.12881","article-title":"Brown adipose tissue activation is not related to hypermetabolism in emphysematous chronic obstructive pulmonary disease patients","volume":"13","author":"Sanders","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E598","DOI":"10.1210\/jc.2010-1957","article-title":"\u03b2-Adrenergic receptor blockade does not inhibit cold-induced thermogenesis in humans: Possible involvement of brown adipose tissue","volume":"96","author":"Wijers","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R987","DOI":"10.1152\/ajpregu.00085.2011","article-title":"SR59230A, a beta-3 adrenergic antagonist, inhibit ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating","volume":"301","author":"Ootsuka","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1080\/21623945.2020.1738792","article-title":"Involvement of calcium channel in the regulation of adipogenesis","volume":"9","author":"Zhai","year":"2020","journal-title":"Adipocyte"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20212491","DOI":"10.1084\/jem.20212491","article-title":"FNIPI regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics","volume":"219","author":"Yin","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.clnu.2009.11.006","article-title":"Loss of adipose tissue and plasma phospholipids: Relationship to survival in advanced cancer patients","volume":"29","author":"Murphy","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jpainsymman.2011.09.010","article-title":"Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: A pilot study","volume":"44","author":"Dalal","year":"2012","journal-title":"J. Pain Symptom Manag."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1017\/S0007114512001067","article-title":"Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: The relationship with diabetes and anaemia","volume":"109","author":"Yang","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/jcb.21964","article-title":"Adipose triglyceride lipase regulates basal lipolysis and lipid droplet size in adipocytes","volume":"105","author":"Miyoshi","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1126\/science.1198973","article-title":"Adipose triglyceride lipase contributes to cancer-associated cachexia","volume":"33","author":"Das","year":"2011","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tsoli, M., Schweiger, M., Vanniasinghe, A.S., Painter, A., Zechner, R., Clarke, S., and Robertson, G. (2014). Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092966"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12944-017-0547-x","article-title":"Lipase and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer","volume":"16","author":"Silverio","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/jcsm.12459","article-title":"Signal regulatory protein alpha initiates cachexia through muscle to adipose tissue crosstalk","volume":"10","author":"Wu","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.isci.2019.05.020","article-title":"Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Tapping and Impairs Brown Adipose Tissue Thermogenesis","volume":"16","author":"Ran","year":"2019","journal-title":"iSciences"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"469","DOI":"10.5114\/ceji.2020.103422","article-title":"Chronic inflammation and the growth hormone\/insulin-like growth factor-1 axis","volume":"45","author":"Pyrzak","year":"2020","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12944-018-0657-0","article-title":"Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose tissue lipolysis and browning","volume":"17","author":"Han","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1530\/eje.0.1380640","article-title":"Modulating effect of human growth hormone on tumour necrosis factor-alpha and interleukin-1beta","volume":"138","author":"Bozzola","year":"1998","journal-title":"Eur. J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.semcdb.2015.09.017","article-title":"PAX3 and PAX7 as Upstream Regulators of Myogenesis","volume":"44","author":"Buckingham","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nrm3265","article-title":"Satellite Cells, the Engines of Muscle Repair","volume":"13","author":"Wang","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1681\/ASN.2010060603","article-title":"Association of Chronic Kidney Disease with Muscle Deficits in Children","volume":"22","author":"Foster","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1681\/ASN.V261130","article-title":"Effects of Recombinant Human Growth Hormone in Adults Receiving Maintenance Gemodialysis","volume":"2","author":"Ziegler","year":"1991","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1053\/ajkd.1998.v32.pm9740162","article-title":"Recombinant Human Growth Hormone Therapy in Malnourished Dialysis Patients: A Randomized Controlled Study","volume":"32","author":"Iglesias","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1046\/j.1523-1755.2001.00971.x","article-title":"Differential Effects of Growth Hormone Therapy in Malnourished Hemodialysis Patients","volume":"60","author":"Kotzmann","year":"2001","journal-title":"Kidney Int."},{"key":"ref_55","first-page":"481","article-title":"Growth Hormone and the Insulin-Like Growth Factor System in Myogenesis","volume":"15","author":"Florini","year":"1996","journal-title":"Endocr. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1038\/s41598-019-39738-6","article-title":"Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation and Functional Outcomes after Chronic Denervation Injury","volume":"9","author":"Lopez","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1093\/jn\/129.4.828","article-title":"Growth Hormone Promotes Somatic and Skeletal Muscle Growth Recovery in Rats Following Chronic-Energy Malnutrition","volume":"129","author":"Gautsch","year":"1999","journal-title":"J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1073\/pnas.0510033103","article-title":"Growth Hormone Promotes Skeletal Muscle Cell Fusion Independent of Insulin-Like Growth Factor 1 Upregulation","volume":"103","author":"Sotiropoulos","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00467-006-0020-y","article-title":"Assessment and treatment of short stature in pediatric patients with chronic kidney disease: A consensus statement","volume":"21","author":"Mahan","year":"2006","journal-title":"Pediatr. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1210\/en.2011-1432","article-title":"Serum IGF-I is not a reliable pharmacodynamic marker of exogenous growth hormone activity in mice","volume":"152","author":"Bielohuby","year":"2011","journal-title":"Endocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1530\/EJE-07-0631","article-title":"Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: A statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia","volume":"157","author":"Ho","year":"2007","journal-title":"Eur. J. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.1073\/pnas.96.12.7088","article-title":"Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice","volume":"96","author":"Sjogren","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00125-009-1402-z","article-title":"Growth hormone improves body composition, fasting blood glucose, glucose tolerance and liver triacylglycerol in a mouse model of diet-induced obesity and type 2 diabetes","volume":"52","author":"List","year":"2009","journal-title":"Diabetologia"},{"key":"ref_64","first-page":"4712","article-title":"Insulin regulation of human hepatic growth hormone receptors: Divergent effects on biosynthesis and surface translocation","volume":"85","author":"Leung","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/0006-291X(78)90177-8","article-title":"Regulation of hepatic growth hormone receptors by insulin","volume":"84","author":"Baxter","year":"1978","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ppul.21436","article-title":"Inflammation and remodeling in infantile, juvenile, and adult allergic sensitized mice","volume":"46","author":"Carnieli","year":"2011","journal-title":"Pediatr. Pulmonol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/intimm\/11.3.445","article-title":"Development of T\u2013B cell collaboration in neonatal mice","volume":"11","author":"Astori","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00429-012-0462-x","article-title":"Cellular composition characterizing postnatal development and maturation of the mouse brain and spinal cord","volume":"218","author":"Fu","year":"2013","journal-title":"Brain Struct. Funct."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00223-003-0101-x","article-title":"Growth of C57BL\/6 mice and the material and mechanical properties of cortical bone from the tibia","volume":"74","author":"Somerville","year":"2004","journal-title":"Calcif. Tissue Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1359\/jbmr.1999.14.12.2159","article-title":"Growing C57BL\/6 mice increase whole bone mechanical properties by increasing geometric and material properties","volume":"14","author":"Brodt","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1359\/jbmr.2002.17.6.1044","article-title":"Changes in bone structure and mass with advancing age in the male C57BL\/6J mouse","volume":"17","author":"Halloran","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_72","first-page":"253067","article-title":"Evaluation of growth patterns and body composition in c57BL\/6J mice using dual energy- X-ray absorptiometry","volume":"2014","author":"Gargiolo","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Loboda, A., Kraft, W.K., Fine, B., Joseph, J., Nebozhyn, M., Zhang, C., He, Y., Yang, X., Wright, C., and Morris, M. (2009). Diurnal variation of the human adipose transcriptome and the link to metabolic disease. BMC Med. Genom., 2.","DOI":"10.1186\/1755-8794-2-7"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2337\/diabetes.55.04.06.db05-0873","article-title":"Characterization of peripheral circadian clocks in adipose tissues","volume":"55","author":"Zvonic","year":"2006","journal-title":"Diabetes"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000500071","article-title":"Effect of circadian rhythm on metabolic processes and the regulation of energy balance","volume":"74","author":"Serin","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.steroids.2011.04.009","article-title":"Effects of ovariectomy and 17-b edstradiol replacement on rat brown adipose tissue mitochondrial function","volume":"76","author":"Proenza","year":"2011","journal-title":"Steroids"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1097\/gme.0b013e318240f6f3","article-title":"The effect of the menopausal transition on body composition and cardiometabolic risk factors: A Montreal-Ottawa New Emerging Team group study","volume":"19","author":"Abdulnour","year":"2012","journal-title":"Menopause"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1210\/endo-103-5-1695","article-title":"Cytoplasmic 17 beta-[3H] estradiol binding in rat adipose tissues","volume":"103","author":"Wade","year":"1978","journal-title":"Endocrinology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1210\/jc.2013-2017","article-title":"Expression and subcellular localization of estrogen receptors \u03b1 and \u03b2 in human fetal brown adipose tissue","volume":"99","author":"Velickovic","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2014.03.031","article-title":"Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK","volume":"20","author":"Martins","year":"2014","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature22342","article-title":"Blocking FSH induces thermogenic adipose tissue and reduces body fat","volume":"546","author":"Liu","year":"2017","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1210\/endo.141.2.7293","article-title":"Opposite Effects of Androgens and Estrogens on Adipogenesis in Rat Preadipocytes: Evidence for Sex and Site-Related Specificities and Possible Involvement of Insulin-Like Growth Factor 1 Receptor and Peroxisome Proliferator-Activated Receptor\u03b3 2","volume":"141","author":"Dieudonne","year":"2000","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1172\/JCI131126","article-title":"Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin activity","volume":"130","author":"Johnson","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Carpentier, A.C., Blondin, D.P., Haman, F., and Richard, D. (2022). Brown adipose tissue\u2014A translational perspective. Endocr. Rev., bnac015.","DOI":"10.1210\/endrev\/bnac015"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:58Z","timestamp":1760146438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,4]]},"references-count":84,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232315310"],"URL":"https:\/\/doi.org\/10.3390\/ijms232315310","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,4]]}}}