Follistatin Promotes Adipocyte Differentiation, Browning, and Energy Metabolism
Open accessAbstract
Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.
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FGF21 and follistatin induce WAT browning directly.
“have also been described to induce WAT browning directly (6).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [185]
The Results section ('Recombinant Fst rescues thermogenic genes and protein levels in Fst KO MEFs'; page unavailable) reports that follistatin treatment increased brown-adipocyte markers in cultured cells. The Discussion describes these as in vitro findings and says further in vivo studies are needed; our copy does not establish direct WAT browning in vivo or address FGF21. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMyostatin plays a pivotal role in adipose tissue plasticity by modulating browning of WAT through AMPK-PGC-1α-FNDC5 axis, a process wherein white adipocytes acquire characteristics of brown adipocytes, including increased mitochondrial content and UCP1 expression, thereby increasing thermogenesis and energy expenditure.
“Myostatin plays a pivotal role in adipose tissue plasticity by modulating the browning of WAT through the AMPK-PGC-1α-FNDC5 axis, a process wherein white adipocytes acquire the characteristics of brown adipocytes, including increased mitochondrial content and the expression of UCP1, thereby increasing thermogenesis and energy expenditure [68,69].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [68]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredFollistatin induces thermogenic genes in murine adipocytes.
“Additionally, it has been shown to induce thermogenic genes in murine adipocytes [185].”
Exercise-induced hepatokines FGF21 and follistatin are upregulated by glucagon.
“the exercise-induced hepatokines FGF21 [43] and follistatin [185], both upregulated by glucagon (5)”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [185]
Citation [185] is attached to the description of follistatin as an exercise-induced hepatokine; glucagon upregulation has a separate citation. The Abstract and Discussion (page numbers unavailable) describe follistatin expression in adipose tissue and its response to differentiation and cold exposure. Searches for exercise, liver secretion, hepatokine, and glucagon found no passage addressing the attributed description. (LLM, conf=0.75)
Experimental — accuracy not yet measuredFST promotes brown adipocyte differentiation in mice.
“FST has also been shown to promote brown adipocyte differentiation in mice [197].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [197]
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“However, several additional factors able to regulate fat browning have been discovered in recent years, such as irisin, fibroblast growth factor 21 (FGF21), follistatin, -aminoisobutyric acid (BAIBA), meteorin-like, PPAR agonists, BMP8B, myostatin, and leptin, among others (25, 28, 230, 252, 258, 260, 291, 336).”
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“, reduction of body fat, improvement of glucose homeostasis and browning of white adipose tissue (WAT)] (Huang et al., 2011; Braga et al., 2014).”
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“5 μM carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) was injected to deduce the maximal respiration capacity (23, 24).”
MethodInfluentialMyokine/Adipokine response to “Aerobic” exercise: Is it just a matter of exercise load?
He, Z., Tian, Y., Valenzuela, P. L., Huang, C., Zhao, J., Hong, P., He, Z., Yin, S., & Lucia, A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00691 · Cited by 59 · see citing works
Orchard, P., Manickam, N., Varshney, A., Vadlamudi, S., Burant, C., Parker, S. C. J., Kaplan, J., Lalancette, C., Mohlke, K. L., Gallagher, K., et al. (2021) · Genome Research · doi:10.1101/gr.268482.120 · Cited by 58 · see citing works
“2020) and overexpression of FST promotes white adipose tissue browning (Braga et al. 2014; Tang et al. 2020).”
BackgroundLee, C. S., Liu, M., Agha, O., Kim, H. T., Feeley, B. T., & Liu, X. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24558 · Cited by 55 · see citing works
“has shown that BAT express high levels of follistatin, a secreted glycoprotein that has high‐affinity binding for activins and myostatin and functions as an inhibitor of myostatin activity.(11,21,22) Previous work has suggested that follistatin is also a soluble mediator of functional interactions between FAP and myog…”
BackgroundRole of exercise-induced hepatokines in metabolic disorders
Ennequin, G., Sirvent, P., & Whitham, M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00433.2018 · Cited by 54 · see citing works
“Recently, it was reported that Fst is highly expressed in the liver 436 but also in skeletal muscle and white and brown adipose tissues (17, 57).”
BackgroundSingh, R., Braga, M., Reddy, S. T., Lee, S.-J., Parveen, M., Grijalva, V., Vergnes, L., & Pervin, S. (2017) · Endocrinology · doi:10.1210/en.2016-1607 · Cited by 54 · see citing works
“We have previously demonstrated that Fst inhibits TGF-b/Smad3 signaling in mouse mesenchymal pluripotent (26) and satellite cells to promote myogenesis (27) and induce brown adipocyte phenotype inMEF primary culture (28).”
BackgroundMethodInfluentialMerlin, J., Evans, B. A., Dehvari, N., Sato, M., Bengtsson, T., & Hutchinson, D. S. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500251 · Cited by 51 · see citing works
“Follistatin is an extracellular protein that functions as an activin- and myostatin-binding protein and inhibits signaling through TGF- superfamily members that regulate diverse processes such as cell growth and differentiation.”
BackgroundRotator cuff tear degeneration and the role of fibro‐adipogenic progenitors
Agha, O., Diaz, A., Davies, M., Kim, H. T., Liu, X., & Feeley, B. T. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14437 · Cited by 52 · see citing works
Rad, M. M., Bijeh, N., Hosseini, S. R. A., & Saeb, A. R. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1829649 · Cited by 51 · see citing works
Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism
Kim, T. H., Hong, D.-G., & Yang, Y. M. (2021) · Biomedicines · doi:10.3390/biomedicines9121903 · Cited by 52 · see citing works
“On the other hand, it has been reported that increased follistatin levels following exercise promote glucose and free fatty acid uptake in skeletal muscle, inducing the differentiation of brown adipocytes [70].”
BackgroundGupta, A., Shamsi, F., Altemose, N., Dorlhiac, G. F., Cypess, A. M., White, A. P., Yosef, N., Patti, M., Tseng, Y.-H., & Streets, A. (2022) · Genome Research · doi:10.1101/gr.275509.121 · Cited by 48 · see citing works
“Enrichment of multiple regulators of adipose tissue development was also detected in cluster 1, such as SEMA5A (Giordano et al. 2001), NPPB (Villarroya and Vidal-Puig 2013), MEST (Karbiener et al. 2015), and FST (Braga et al. 2014), further suggesting the existence of adipogenic commitment activity in this cell popula…”
Bone Regulates Browning and Energy Metabolism Through Mature Osteoblast/Osteocyte PPARγ Expression
Brun, J., Berthou, F., Trajkovski, M., Maechler, P., Foti, M., & Bonnet, N. (2017) · Diabetes · doi:10.2337/db17-0116 · Cited by 47 · see citing works
“Its regulation through the PPARs, and particularly, PPARg has been put forward not only in adipose tissue (12,13) but also in liver and skeletal muscle, where it controls the production of several hepatokines (14) and myokines, respectively (15,16).”
BackgroundPervin, S., Reddy, S. T., & Singh, R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.653179 · Cited by 42 · see citing works
“First insight regarding a direct role for FST in adipose tissues was obtained from analysis of Fst gene expression of a tissue panel from C57BL6/J mice that included WAT (inguinal subcutaneous and epididymal) and BAT depots, as well as several other metabolic tissues including brain, heart, intestine, liver, skeletal…”
BackgroundResultInfluentialSelf-citationFeeley, B. T., Liu, M., Benjamin, C., Agha, O., Aung, M. S., Lee, C. S., & Liu, X. (2020) · The American Journal of Sports Medicine · doi:10.1177/0363546520935855 · Cited by 42 · see citing works
“These findings confirm previous studies’ demonstration of beige fat follistatin expression.(2,44) These data suggest a possible functional role of FAPs in the ability to improve muscle quality after RC repair if directed toward a more beneficial phenotype as opposed to their usual white adipocyte and fibroblast fates.”
BackgroundMethodResultTero-Vescan, A., Degens, H., Matsakas, A., Ștefănescu, R., Ősz, B. E., & Slevin, M. (2025) · Pharmaceuticals · doi:10.3390/ph18081222 · Cited by 44 · see citing works
“…by modulating the browning of WAT through the AMPK-PGC-1 α -FNDC5 axis, a process wherein white adipocytes acquire the characteristics of brown adipocytes, including increased mitochondrial content and the expression of UCP1, thereby increasing thermogenesis and energy expenditure [68,69].”
Brown adipose tissue-derived metabolites and their role in regulating metabolism
Ziqubu, K., Dludla, P. V., Mabhida, S. E., Jack, B. U., Keipert, S., Jastroch, M., & Mazibuko-Mbeje, S. E. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155709 · Cited by 40 · see citing works
Brown and beige adipose tissues: phenotype and metabolic potential in mice and men
Chechi, K., Lichtenbelt, W. D. V. M., & Richard, D. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00021.2017 · Cited by 39 · see citing works
“In addition, multiple other myokines and adipokines, such as myostatin (139), follistatin (17), IL-6 (117), -aminoisobutyric acid (127), and fibroblast growth factor 21 (51), have been shown to regulate browning of WAT in rodent models.”
BackgroundThe glycoprotein follistatin-like 1 promotes brown adipose thermogenesis
Fang, D., Shi, X., Lu, T., Ruan, H., & Gao, Y. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.008 · Cited by 39 · see citing works
The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn’s Disease
Monfort-Ferré, D., Caro, A., Menacho, M., Martí, M., Espina, B., Boronat-Toscano, A., Nuñez-Roa, C., Seco, J., Bautista, M., Espín, E., et al. (2022) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjac069 · Cited by 38 · see citing works
“In the present study we report, for the first time to our knowledge, a browning phenotype in the creeping fat and other AT depots of patients with active CD. Creeping fat is a recognized source of adipocyte-produced soluble factors including inflammatory and anti-inflammatory cytokines; 46,47 however, the cell types i…”
InfluentialThe orphan ligand, activin C, signals through activin receptor-like kinase 7
Goebel, E. J., Ongaro, L., Kappes, E. C., Vestal, K., Belcheva, E., Castonguay, R., Kumar, R., Bernard, D. J., & Thompson, T. B. (2022) · eLife · doi:10.7554/elife.78197 · Cited by 34 · see citing works
Hormonal Regulation of Adipogenesis
Lee, M. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160047 · Cited by 42 · see citing works
Aging and Immunometabolic Adaptations to Thermogenesis
Lettieri‐Barbato, D., & Aquilano, K. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101143 · Cited by 33 · see citing works
Klingenspor, M., & Fromme, T. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0965-6_3 · Cited by 30 · see citing works
Agha, O., Mueller‐Immergluck, A., Liu, M., Zhang, H., Theologis, A. A., Clark, A., Kim, H. T., Liu, X., Feeley, B. T., & Bailey, J. F. (2020) · JOR Spine · doi:10.1002/jsp2.1091 · Cited by 29 · see citing works
Impact of adipokines and myokines on fat browning
Rodrı́guez, A., Catalán, V., Ramírez, B., Unamuno, X., Portincasa, P., Gómez‐Ambrosi, J., Frühbeck, G., & Becerril, S. (2020) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00736-2 · Cited by 30 · see citing works
“In this regard, follistatin enhances the acquisition of brown adipocyte characteristics, by inducing the expression of key brown adipose-associated markers (Pgc1a, Ucp1, Prdm16 and Fabp4) as well as increasing cellular oxygen consumption [13].”
BackgroundExercise‐Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism
Al‐Ibraheem, A. M. T., Hameed, A. A. Z., Marsool, M. D. M., Jain, H., Prajjwal, P., Khazmi, I., Nazzal, R., Al-Najati, H. M. H., Al‐Zuhairi, B. H. Y. K., Razzaq, M., et al. (2024) · Health Science Reports · doi:10.1002/hsr2.70034 · Cited by 33 · see citing works
“…dimer of myostatin and prevents it from interacting to receptors, 28 and its function in binding to, and inhibiting the activity of the superfamily of TGF ‐ β , 29 FST may play a role in adipose tissue metabolism as both myostatin and TGF ‐ β play a role in adipose tissue metabolism and obesity.”
BackgroundMyostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis
Li, N., Yang, Q., Walker, R. G., Thompson, T. B., Du, ., & Rodgers, B. D. (2015) · Endocrinology · doi:10.1210/en.2015-1546 · Cited by 29 · see citing works
“28) and can induce adipose browning (29) either due to the”
BackgroundSingh, R., Pervin, S., Lee, S., Kuo, A., Grijalva, V. R., David, J., Vergnes, L., & Reddy, S. T. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s159315 · Cited by 29 · see citing works
“7 Since AdipoQ has been reported to be a downstream effector of FGF21, 42 a well-known adipose browning and important regulator of key metabolic functions, 43–46 we explored the potential role of FGF21/AdipoQ/pAMPK signaling pathway in eliciting Fst metabolic actions in both Epi and SC adipose…”
InfluentialLi, H., Zhang, C., Liu, J., Xie, W., Xu, W., Liang, F., Huang, K., & He, X. (2019) · PLoS ONE · doi:10.1371/journal.pone.0220310 · Cited by 26 · see citing works
Hulmi, J. J., Nissinen, T. A., Penna, F., & Bonetto, A. (2021) · Cells · doi:10.3390/cells10030516 · Cited by 23 · see citing works
“In addition, white adipose tissue browning, which has been suggested to happen in cancer cachexia and to contribute to the progression of cachexia [180], may also be increased in some situations by blocking ACVR2 ligands [193].”
BackgroundKlingenspor, M., Bast‐Habersbrunner, A., Bolze, F., Li, Y., Maurer, S., Schweizer, S., Willershäuser, M., & Fromme, T. (2017) · Springer eBooks · doi:10.1007/978-3-319-52031-5_4 · Cited by 21 · see citing works
Influence of Nutritional Status and Physical Exercise on Immune Response in Metabolic Syndrome
Lombardo, M., Feraco, A., Bellia, C., Prisco, L., D’Ippolito, I., Padua, E., Storz, M. A., Lauro, D., Caprio, M., & Bellia, A. (2022) · Nutrients · doi:10.3390/nu14102054 · Cited by 21 · see citing works
“Its action is in fact regulated by the presence of follistatin, which is produced by the liver in response to physical activity and is known to antagonize MSTN, promoting browning both in vitro and in vivo [142].”
BackgroundManagement of Oxidative Stress: Crosstalk Between Brown/Beige Adipose Tissues and Skeletal Muscles
Pan, R., & Chen, Y. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.712372 · Cited by 22 · see citing works
Follistatin Attenuates Myocardial Fibrosis in Diabetic Cardiomyopathy via the TGF-β–Smad3 Pathway
Wang, Y., Yu, K., Zhao, C., Zhou, L., Cheng, J. R., Wang, D. W., & Zhao, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.683335 · Cited by 19 · see citing works
Villarroya, F., Gavaldà‐Navarro, A., Peyrou, M., Villarroya, J., & Giralt, M. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_119 · Cited by 19 · see citing works
Pan, J., Nilsson, J. Å., Engström, G., & Marinis, Y. Z. D. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.09.012 · Cited by 18 · see citing works
Tsompanidis, A., Vafiadaki, E., Blüher, S., Kalozoumi, G., Sanoudou, D., & Mantzoros, C. S. (2016) · Metabolism · doi:10.1016/j.metabol.2016.03.005 · Cited by 18 · see citing works
“More recently, follistatin administration was found to induce the differentiation of white adipose tissue to the “brite” type, which has greater thermogenic capacity, increased respiratory function and an active role in energy metabolism [21].”
BackgroundVarshney, A., Manickam, N., Orchard, P., Tovar, A., Ventresca, C., Zhang, Z., Feng, F., Mears, J., Erdos, M. R., Narisu, N., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.15.571696 · Cited by 18 · see citing works
Role of Distinct Fat Depots in Metabolic Regulation and Pathological Implications
Sahu, B., Tikoo, O., Pati, B., Senapati, U., & Bal, N. C. (2022) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2022_73 · Cited by 15 · see citing works
Garcés, M. F., Vallejo, S. A., Sánchez, E., Palomino‐Palomino, M. A., Leal, L. G., Ángel‐Müller, E., Díaz-Cruz, L. A., Ruíz‐Parra, A. I., Clavijo, A. ́. G., Castano, J. P., et al. (2015) · Clinical Endocrinology · doi:10.1111/cen.12715 · Cited by 15 · see citing works
Tao, R., Stöhr, O., Wang, C., Qiu, W., Copps, K. D., & White, M. F. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101703 · Cited by 14 · see citing works
“It has been suggested that Fst promotes the production of both beige adipose and BAT, which can increase EE and reduce body weight [59]; however, LDKO mice display acute cold intolerance and reduced thermogenic gene expression in BAT and WAT, owing at least in part to low hepatic Fgf21 levels [33].”
BackgroundMolecular and cellular regulation of thermogenic fat
Wang, C., Wang, X., & Hu, W. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1215772 · Cited by 14 · see citing works
Follistatin Alleviates Hepatic Steatosis in NAFLD via the mTOR Dependent Pathway
Tong, J., Cong, L., Jia, Y., He, A. B.-L., Guo, Y., He, J., Li, D., Zou, B., & Li, J. (2022) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s380053 · Cited by 14 · see citing works
“FST can promote the differentiation and browning of adipocytes, and mitigate systemic metabolic inflammation.(24) FST gene therapy could be used to prevent high-fat diet (HFD)-induced obesity and systemic metabolic inflammation in the mice model.”
BackgroundFollistatin and follistatin-like 3 in metabolic disorders
Bielka, W., Przezak, A., & Pawlik, A. (2023) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2023.106785 · Cited by 15 · see citing works
Leyden, G. M., Greenwood, M. P., Gaborieau, V., Han, Y., Amos, C. I., Brennan, P., Murphy, D., Smith, G. D., & Richardson, T. G. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-02060-6 · Cited by 13 · see citing works
Jang, J., Jung, Y., Chae, S., Cho, S. H., Yoon, M., Yang, H., Shin, S. S., & Yoon, Y. (2017) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2017.08.024 · Cited by 13 · see citing works
Pervin, S., Singh, V., Tucker, A., Collazo, J., & Singh, R. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0036 · Cited by 13 · see citing works
“Based on Fst’s established inhibitory actions on Mst/TGF-β signaling and its induction during negative energy balance, it was hypothesized that Fst may regulate adipose browning and energy metabolism [85].”
BackgroundJürimäe, J., Vaiksaar, S., Purge, P., & Tillmann, V. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.689696 · Cited by 12 · see citing works
Robic, A., Fève, K., Riquet, J., & Prunier, A. (2016) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2016.03.008 · Cited by 12 · see citing works
Jing Hua, H. U., Li, X., Tian, W., Lu, Y., Xu, Y., Wang, F., Qin, W., Ma, X., Puno, P., & Xiong, W. (2019) · Molecules · doi:10.3390/molecules24010158 · Cited by 11 · see citing works
“The murine 3T3-L1 cells and mouse embryonic fibroblasts (MEFs), in vitro models, have proved useful for studying this process [11,12].”
BackgroundPark, M.-J., Lee, J., Bagon, B. B., Matienzo, M. E., Lee, C., Kim, K., & Kim, D. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167055 · Cited by 11 · see citing works
Cao, Q., Zhang, J., Yu, Q., Wang, J., Dai, M., Zhang, Y., Luo, Q., & Bao, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m091256 · Cited by 11 · see citing works
“Liver sections were stained using the Oil Red O work solutions containing 6 ml of Oil Red O stock solution (G1015; Servicebio) and 4 ml of ddH2O for 15 min as previously described (25).”
MethodZhu, B., Wang, T., Niu, Q., Wang, Z., Hay, E. H., Xu, L., Chen, Y., Zhang, L., Gao, H., Gao, H., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-07604-z · Cited by 10 · see citing works
“The notable upregulation after post-interference was observed in genes such as FEM1A , ESRP2 , PARVB , STX1A , and RGMA , while CCNE2 , FXN , PDCD6 , PLIN2 , FST and TSPAN12 were signi fi cantly downregulated (Fig.”
Schalt, A., Johannsen, M., Kim, J., Chen, R., Murphy, C. J., Coker, M. S., Gunga, H., Coker, R. H., & Steinach, M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01761 · Cited by 10 · see citing works
Nunes, H. C., Tavares, S. C., Garcia, H. V., Cucielo, M. S., dos Santos, S. A. A., Aal, M. C. E., Golim, M. D. A., Justulin, L. A., Ribeiro, A. D. O., Deffune, E., et al. (2022) · Environmental Toxicology · doi:10.1002/tox.23598 · Cited by 10 · see citing works
“Genotoxicity was assessed at day seven and a single-cell gel electrophoresis (comet) assay was performed according to Braga et al.15 and Singh et al.66 Briefly, electro- phoresis was conducted for 20min at 25 V and 300mA; the slides were then neutralized with 0.4 M tris HCl solution (pH 7.5) for 15min and fixed with 1…”
BackgroundMethodInfluentialVestal, K. A., Kattamuri, C., Koyiloth, M., Ongaro, L., Howard, J. A., Deaton, A. M., Ticau, S., Dubey, A., Bernard, D. J., & Thompson, T. B. (2024) · Biochemical Journal · doi:10.1042/bcj20230404 · Cited by 10 · see citing works
Zhang, C., Wang, J. J., He, X., Wang, C., Zhang, B., Xu, J., Xu, W., Luo, Y., & Huang, K. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000496042 · Cited by 9 · see citing works
Gui, C., & Meyer, G. A. (2024) · Journal of Orthopaedic Research® · doi:10.1002/jor.25933 · Cited by 8 · see citing works
Molecular epigenetics in the transition of white to brown fat
Chaturvedi, S., Chaturvedi, P., Gupta, P. C., Awasthi, S. K., & Kalani, A. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156073 · Cited by 8 · see citing works
Pham, T. C. P., Bojsen-Møller, K. N., Madsbad, S., Wojtaszewski, J. F. P., Richter, E. A., & Sylow, L. (2020) · International Journal of Obesity · doi:10.1038/s41366-020-00664-7 · Cited by 8 · see citing works
Hormonal Regulation of Adipogenesis
Lee, M. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00782.x · Cited by 7 · see citing works
“Follistatin is highly expressed in brown and inguinal fat in mice, is induced during adipogenesis and promotes differentiation as well as thermo-genic gene expression in brown adipocytes (34).”
The Reign of Follistatin in Tumors and Their Microenvironment: Implications for Drug Resistance
Sosa, J., Oyelakin, A., & Sinha, S. (2024) · Biology · doi:10.3390/biology13020130 · Cited by 7 · see citing works
Lipoxin A4 promotes adipogenic differentiation and browning of mouse embryonic fibroblasts
Wang, Q., Jin, F., Zhang, J., Li, Z., & Yu, D. S. (2021) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-021-00617-y · Cited by 7 · see citing works
The effect of TGFβ1 on thermogenic markers is dependent on the degree of adipocyte differentiation
Maharjan, B. R., McLennan, S. V., Twigg, S. M., & Williams, P. F. (2020) · Bioscience Reports · doi:10.1042/bsr20194262 · Cited by 6 · see citing works
“Others have suggested that TGF β can regulate the production of brite or beige progenitor cells in WAT [6–8].”
Tseng, F., Chen, Y.-T., Chi, Y.-C., Chen, P., & Yang, W. (2016) · Medicine · doi:10.1097/md.0000000000002661 · Cited by 5 · see citing works
Getting the Skinny on Follistatin and Fat
Li, J.-X., & Cummins, C. L. (2017) · Endocrinology · doi:10.1210/en.2017-00223 · Cited by 5 · see citing works
“Mouse embryonic fibroblast (MEF) cultures from follistatin knockout (Fst KO) mice were found to have decreased expression of genes involved in lipid and energy metabolism as well as BAT-specific markers compared with wild-type (WT) MEFs when undergoing adipogenic differentiation (19).”
BackgroundInfluentialZabolotneva, A. A., Popruga, K. E., Makarov, V. V., Yudin, S. M., Михайлович, Г. А., Roumiantsev, S. A., & Shestopalov, A. V. (2025) · Biomedicines · doi:10.3390/biomedicines13010183 · Cited by 4 · see citing works
“Additionally, earlier research has shown that adipogenic cells from mstn − / − mice exhibit increased protein expression of markers specific to mature adipocytes, such as adiponectin, AMP-activated protein kinase, PPAR γ , and leptin [55–57].”
Cao, M., & Cui, B. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02222-1 · Cited by 5 · see citing works
“FST can promote the differentiation and browning of adipocytes and mitigate systemic metabolic inflammation [64, 65].”
BackgroundCan Exercise-Mediated Adipose Browning Provide an Alternative Explanation for the Obesity Paradox?
Zhao, J., Li, X., Liang, C., & Yan, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051790 · Cited by 4 · see citing works
Jürimäe, J., Remmel, L., Tamm, A., Purge, P., Maasalu, K., & Tillmann, V. (2023) · Children · doi:10.3390/children10071226 · Cited by 4 · see citing works
“Follistatin exerts metabolic benefits by reducing adiposity and improving glucose metabolism [28,29].”
BackgroundCerabino, N., Bonfiglio, C., Chito, M. D., Donvito, R., Mongelli, F. P., Pesole, P. L., Stabile, D., Shahini, E., Zappimbulso, M., Cozzolongo, R., et al. (2025) · Nutrients · doi:10.3390/nu17132124 · Cited by 3 · see citing works
“Furthermore, follistatin promotes the browning of white adipose tissue, leading to increased thermogenesis and energy expenditure [11].”
Fung, R. S. K., Bai, J., He, M., Yuen, K. W. Y., & Wong, A. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00211 · Cited by 3 · see citing works
“In general, activin and its binding protein follistatin are widely expressed in various tissues and play a role in diverse functions including folliculogenesis (9), spermatogenesis (10), implantation and pregnancy (11, 12), regulation of pituitary hormones (13), energy metabolism (14), adipocyte differentiation (15),…”
BackgroundPervin, S., Wilson, N. Y. A. H., Reddy, S. T., & Singh, R. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88294 · Cited by 3 · see citing works
“Significantly lower basal mitochondrial respiration in Fst KO MEFs compared to the WT cultures was rescued by exogenous recombinant Fst, suggesting that Fst increases cellular respiration [11].”
BackgroundMethodInfluentialGupta, A., Shamsi, F., Altemose, N., Dorlhiac, G., Cypess, A. M., White, A. P., Patti, M., Tseng, Y., & Streets, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.24.435852 · Cited by 3 · see citing works
“Transforming growth factor superfamily genes BMP4 and TGFB2 were also enriched in cluster 1, along with regulators of adipose tissue development SEMA5A, MEST, and FST (Table S2B).”
Gene Therapy Approach for Treatment of Obese Agouti Mice
Yunin, M. A., Boychenko, S. S., Lebedev, P., Deykin, A. V., Покровский, М. В., & Egorov, A. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212144 · Cited by 2 · see citing works
- Authors
- Braga, M., Reddy, S. T., Vergnes, L., Pervin, S., Grijalva, V., Stout, D., David, J., Li, X., Tomasian, V., Reid, C. B., Norris, K. C., Devaskar, S. U., Reue, K., & Singh, R.
- Affiliations
- Charles R. Drew University of Medicine and Science (US)
- University of California, Los Angeles (US)
- Corresponding author
- Singh, Rajan
- ORCID
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 55
- Issue
- 3
- Pages
- 375-384
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3934723
- OpenAlex
- W2143024501
- Cited by
- 111
- References
- 51
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 13 · 2018: 7 · 2017: 12 · 2016: 6 · 2015: 8 · 2014: 1
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (SC1AG033407, SC1AG049682)
- National Heart, Lung, and Blood Institute (P01HL090553, R01 HL-71776, R01HL071776, P01HL028481)
- National Cancer Institute (SC1CA165865, SC1CA1658650-01A1)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD041230)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- follistatin, brown adipose tissue, adipogenesis, energy metabolism, thermogenesis, UCP1, PPARγ coactivator-1α, paracrine signaling, cold-induced thermogenesis, cellular respiration, embryonic fibroblasts
- MeSH terms
- Animals, Adipose Tissue, Brown, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cell Differentiation, Cells, Cultured, Cold Temperature, Embryo, Mammalian, Energy Metabolism, Female, Fibroblasts, Male, Mice, Inbred C57BL, Oxygen Consumption, Immunoblotting, Adipocytes, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Thermogenesis, Follistatin, Lipid Metabolism, Mice, Proton Ionophores
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