Modulation of Transforming Growth Factor-β/follistatin Signaling and White Adipose Browning: Therapeutic Implications for Obesity Related Disorders

Overview

Journal Horm Mol Biol Clin Investig

Publisher De Gruyter

Specialty Biochemistry

Date 2017 Sep 10

PMID 28888087

Citations 9

Authors

Shehla Pervin

Vineeta Singh

Alexandria Tucker

Javier Collazo

Rajan Singh

Affiliations

Soon will be listed here.

Abstract

Obesity is a major risk factor for the development of diabetes, insulin resistance, dyslipidemia, cardiovascular disease and other related metabolic conditions. Obesity develops from perturbations in overall cellular bioenergetics when energy intake chronically exceeds total energy expenditure. Lifestyle interventions based on reducing total energy uptake and increasing activities including exercise have proved ineffective in the prevention and treatment of obesity because of poor adherence to such interventions for an extended period of time. Brown adipose tissue (BAT) has an extraordinary metabolic capacity to burn excess stored energy and holds great promise in combating obesity and related diseases. This unique ability to nullify the effects of extra energy intake of these specialized tissues has provided attractive perspectives for the therapeutic potential of BAT in humans. Browning of white adipose tissue by promoting the expression and activity of key mitochondrial uncoupling protein 1 (UCP1) represents an exciting new strategy to combat obesity via enhanced energy dissipation. Members of the transforming growth factor-beta (TGF-β) superfamily including myostatin and follistatin have recently been demonstrated to play a key role in regulating white adipose browning both in in-vitro and in-vivo animal models and thereby present attractive avenues for exploring the therapeutic potential for the treatment of obesity and related metabolic diseases.

Citing Articles

Gene Therapy Approach for Treatment of Obese Agouti Mice.

Yunin M, Boychenko S, Lebedev P, Deykin A, Pokrovskii M, Egorov A Int J Mol Sci. 2024; 25(22.

PMID: 39596212 PMC: 11594101. DOI: 10.3390/ijms252212144.

Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.

Chrisochoidou Y, Roy R, Farahmand P, Gonzalez G, Doig J, Krasny L Cell Death Dis. 2023; 14(11):725.

PMID: 37938546 PMC: 10632403. DOI: 10.1038/s41419-023-06240-x.

Plasma Myostatin Increases with Age in Male Youth and Negatively Correlates with Vitamin D in Severe Pediatric Obesity.

Baumgartner M, Lischka J, Schanzer A, de Gier C, Walleczek N, Greber-Platzer S Nutrients. 2022; 14(10).

PMID: 35631274 PMC: 9144022. DOI: 10.3390/nu14102133.

The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn's Disease.

Monfort-Ferre D, Caro A, Menacho M, Marti M, Espina B, Boronat-Toscano A J Crohns Colitis. 2022; 16(10):1571-1583.

PMID: 35554517 PMC: 9624294. DOI: 10.1093/ecco-jcc/jjac069.

Deciphering the Causal Relationships Between Low Back Pain Complications, Metabolic Factors, and Comorbidities.

Tarabeih N, Kalinkovich A, Shalata A, Cherny S, Livshits G J Pain Res. 2022; 15:215-227.

PMID: 35125889 PMC: 8809521. DOI: 10.2147/JPR.S349251.

References

Bartelt A, Bruns O, Reimer R, Hohenberg H, Ittrich H, Peldschus K . Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011; 17(2):200-5. DOI: 10.1038/nm.2297. View

Braga M, Pervin S, Norris K, Bhasin S, Singh R . Inhibition of in vitro and in vivo brown fat differentiation program by myostatin. Obesity (Silver Spring). 2013; 21(6):1180-8. PMC: 3735638. DOI: 10.1002/oby.20117. View

Wankhade U, Shen M, Yadav H, Thakali K . Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue. Biomed Res Int. 2017; 2016:2365609. PMC: 5220392. DOI: 10.1155/2016/2365609. View

Vijgen G, Bouvy N, Teule G, Brans B, Hoeks J, Schrauwen P . Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012; 97(7):E1229-33. DOI: 10.1210/jc.2012-1289. View

Galgani J, Ravussin E . Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond). 2009; 32 Suppl 7:S109-19. PMC: 2897177. DOI: 10.1038/ijo.2008.246. View

Kozak L . The genetics of brown adipocyte induction in white fat depots. Front Endocrinol (Lausanne). 2012; 2:64. PMC: 3356051. DOI: 10.3389/fendo.2011.00064. View

Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y . Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring). 2010; 19(1):13-6. DOI: 10.1038/oby.2010.105. View

Long J, Svensson K, Tsai L, Zeng X, Roh H, Kong X . A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014; 19(5):810-20. PMC: 4052772. DOI: 10.1016/j.cmet.2014.03.025. View

Zhou Z, Toh S, Chen Z, Guo K, Peng Ng C, Ponniah S . Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat Genet. 2003; 35(1):49-56. DOI: 10.1038/ng1225. View

10.

Liu W, Bi P, Shan T, Yang X, Yin H, Wang Y . miR-133a regulates adipocyte browning in vivo. PLoS Genet. 2013; 9(7):e1003626. PMC: 3708806. DOI: 10.1371/journal.pgen.1003626. View

11.

Yilmaz Y, Ones T, Purnak T, Ozguven S, Kurt R, Atug O . Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans. Aliment Pharmacol Ther. 2011; 34(3):318-23. DOI: 10.1111/j.1365-2036.2011.04723.x. View

12.

Stanford K, Middelbeek R, Townsend K, An D, Nygaard E, Hitchcox K . Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2012; 123(1):215-23. PMC: 3533266. DOI: 10.1172/JCI62308. View

13.

Fournier B, Murray B, Gutzwiller S, Marcaletti S, Marcellin D, Bergling S . Blockade of the activin receptor IIb activates functional brown adipogenesis and thermogenesis by inducing mitochondrial oxidative metabolism. Mol Cell Biol. 2012; 32(14):2871-9. PMC: 3416189. DOI: 10.1128/MCB.06575-11. View

14.

Braga M, Bhasin S, Jasuja R, Pervin S, Singh R . Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action. Mol Cell Endocrinol. 2011; 350(1):39-52. PMC: 3264813. DOI: 10.1016/j.mce.2011.11.019. View

15.

Feldman B, Streeper R, Farese Jr R, Yamamoto K . Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. Proc Natl Acad Sci U S A. 2006; 103(42):15675-80. PMC: 1592529. DOI: 10.1073/pnas.0607501103. View

16.

Hoeke G, Kooijman S, Boon M, Rensen P, Berbee J . Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis. Circ Res. 2016; 118(1):173-82. DOI: 10.1161/CIRCRESAHA.115.306647. View

17.

Lo K, Sun L . Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes. Biosci Rep. 2013; 33(5). PMC: 3764508. DOI: 10.1042/BSR20130046. View

18.

Craft C, Pietka T, Schappe T, Coleman T, Combs M, Klein S . The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGF-β. Diabetes. 2014; 63(6):1920-32. PMC: 4030109. DOI: 10.2337/db13-1604. View

19.

Liu D, Black B, Derynck R . TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 2001; 15(22):2950-66. PMC: 312830. DOI: 10.1101/gad.925901. View

20.

Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y . Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2013; 63(2):514-25. DOI: 10.2337/db13-1106. View