Nicotine induces a dual effect on the beige-like phenotype in adipocytes
Keywords:nicotine, beige adipocytes, beige-like dysfunction, different differentiation stages, 3T3-L1
- The influence of nicotine on the beige-like phenotype in adipocytes has not been examined.
- We detected the expression of beige-related genes and proteins at different stages of differentiation of the preadipocyte 3T3-L1 cell line.
- Nicotine, acting on different stages of 3T3-L1 differentiation, produced a dual effect on the expression of beige-related genes and proteins, inducing dysfunction in beige-like adipocytes.
- This activity can affect thermogenesis in adipose tissue and cause dysfunctional fat metabolism.
Abstract: Nicotine, the main component of cigarette smoke, affects white/brown adipocytes. Few studies have concentrated on beige adipocytes. In this study, 3T3-L1 cells were differentiated in the presence of nicotine (25, 50 and 100 µmol/L) during early differentiation and maintenance stages. Cell viability and the state of lipid droplets were assessed by the MTT assay and Oil Red O, respectively, and the expression of beige-related genes and proteins was examined by RT-qPCR, Western blotting and flow cytometry. Nicotine did not alter adipocyte differentiation; however, it increased the expression of peroxisome proliferator-activated receptor gamma (PPARγ) protein during early differentiation and maintenance. Nicotine treatment during early differentiation downregulated gene and protein expression of PPARγ coactivator 1-alpha (PGC-1α), uncoupling protein 1 (UCP1) and cluster of differentiation 137 (CD137), and gene expression of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1 (Cited1), transmembrane protein 26 (Tmem26), and short stature homeobox 2 (Shox2). Nicotine treatment during the maintenance stage upregulated these beige-related genes/proteins. Nicotine treatment of immature adipocytes damaged beige function through a decrease in PGC-1α/UCP1 expression, but nicotine treatment of mature adipocytes or both immature and mature cells enhanced beige functioning. Nicotine induced beige-like phenotype dysfunction in 3T3-L1 adipocytes. This process may affect thermogenesis in adipose tissue and cause a dysfunction in fat metabolism.
Received: April 3, 2019; Revised: June 10, 2019; Accepted: June 14, 2019; Published online: July 6, 2019
How to cite this article: Chen H, Xiang J, Zhang W, Sun A, Li G, Yan Y. Nicotine induces a dual effect on the beige-like phenotype in adipocytes. Arch Biol Sci. 2019;71(3):533-40.
Wipfli HL, Samet JM. Second-hand smoke's worldwide disease toll. Lancet. 2011;377(9760):101-2.
Somm E, Schwitzgebel VM, Vauthay DM, Camm EJ, Chen CY, Giacobino JP, Sizonenko SV, Aubert ML, Huppi PS. Prenatal nicotine exposure alters early pancreatic islet and adipose tissue development with consequences on the control of body weight and glucose metabolism later in life. Endocrinology. 2008;149(12):6289-99.
Liu M, Chuang Key CC, Weckerle A, Boudyguina E, Sawyer JK, Gebre AK, Spoo W, Makwana O, Parks JS. Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice. Food Chem Toxicol. 2018;113:287-95.
Kim SH, Plutzky J. Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders. Diabetes Metab J. 2016;40(1):12-21.
Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366-76.
Gao YJ, Holloway AC, Zeng ZH, Lim GE, Petrik JJ, Foster WG, Lee RM. Prenatal exposure to nicotine causes postnatal obesity and altered perivascular adipose tissue function. Obes Res. 2005;13(4):687-92.
Yoshida T, Sakane N, Umekawa T, Kogure A, Kondo M, Kumamoto K, Kawada T, Nagase I, Saito M. Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice. Int J Obes Relat Metab Disord. 1999;23(6):570-5.
Green H, Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell. 1974;3(2):127-33.
An Z, Wang H, Song P, Zhang M, Geng X, Zou MH. Nicotine-induced activation of AMP-activated protein kinase inhibits fatty acid synthase in 3T3L1 adipocytes: a role for oxidant stress. J Biol Chem. 2007;282(37):26793-801.
Bai XJ, Fan LH, He Y, Ren J, Xu W, Liang Q, Li HB, Huo JH, Bai L, Tian HY, Fan FL, Ma AQ. Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel. Nutrition. 2016;32(6):645-8.
Lone J, Parray HA, Yun JW. Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1 adipocytes. Biochimie. 2018;146:97-104.
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-39.
Sharp LZ, Shinoda K, Ohno H, Scheel DW, Tomoda E, Ruiz L, Hu H, Wang L, Pavlova Z, Gilsanz V, Kajimura S. Human BAT possesses molecular signatures that resemble beige/brite cells. PloS One. 2012;7(11):e49452.
Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, Virtanen KA, Beuschlein F, Persson A, Borga M, Enerback S. Evidence for two types of brown adipose tissue in humans. Nat Med. 2013;19(5):631-4.
Pei Y, Jiao Z, Dong W, Pei L, He X, Wang H, Xu D. Excitotoxicity and compensatory upregulation of GAD67 in fetal rat hippocampus caused by prenatal nicotine exposure are associated with inhibition of the BDNF pathway. Food Chem Toxicol. 2019; 123:314-25.
An Z, Wang H, Song P, Zhang M, Geng X, Zou MH. Nicotine-induced activation of AMP-activated protein kinase inhibits fatty acid synthase in 3T3L1 adipocytes: a role for oxidant stress. J Biol Chem. 2007; 282(37):26793-801.
La Merrill M, Emond C, Kim MJ, Antignac JP, Le Bizec B, Clement K, Birnbaum LS, Barouki R. Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect. 2013;121(2):162-9.
Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252-63.
Asano H, Kanamori Y, Higurashi S, Nara T, Kato K, Matsui T, Funaba M. Induction of beige-like adipocytes in 3T3-L1 cells. J Vet Med Sci. 2014; 76(1):57-64.
Okamatsu-Ogura Y, Fukano K, Tsubota A, Uozumi A, Terao A, Kimura K, Saito M. Thermogenic ability of uncoupling protein 1 in beige adipocytes in mice. PloS One. 2013;8(12):e84229.
Seoane-Collazo P, Martinez de Morentin PB, Ferno J, Dieguez C, Nogueiras R, Lopez M. Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats. Endocrinology. 2014;155(5):1679-89.
Arai K, Kim K, Kaneko K, Iketani M, Otagiri A, Yamauchi N, Shibasaki T. Nicotine infusion alters leptin and uncoupling protein 1 mRNA expression in adipose tissues of rats. Am J Physiol Endocrinol Metab. 2001;280(6):E867-76.
Zhang H, Zhu L, Bai M, Liu Y, Zhan Y, Deng T, Yang H, Sun W, Wang X, Zhu K, Fan Q, Li J, Ying G, Ba Y. Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR-133/PRDM16 pathway. Int J Cancer. 2019;144(10):2501-15.
Villanueva CJ, Waki H, Godio C, Nielsen R, Chou WL, Vargas L, Wroblewski K, Schmedt C, Chao LC, Boyadjian R, Mandrup S, Hevener A, Saez E, Tontonoz P. TLE3 is a dual-function transcriptional coregulator of adipogenesis. Cell Metab. 2011;13(4):413-27.
Santos GM, Neves Fde A, Amato AA. Thermogenesis in white adipose tissue: An unfinished story about PPARgamma. Biochim Biophys Acta. 2015;1850(4):691-5.
Villanueva CJ, Vergnes L, Wang J, Drew BG, Hong C, Tu Y, Hu Y, Peng X, Xu F, Saez E, Wroblewski K, Hevener AL, Reue K, Fong LG, Young SG, Tontonoz P. Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPARγ specifies lipid storage versus thermogenic gene programs. Cell Metab. 2013; 17(3):423-35.
Wang Z, Wang D, Wang Y. Cigarette Smoking and Adipose Tissue: The Emerging Role in Progression of Atherosclerosis. Mediators Inflamm. 2017;2017:3102737.
Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79(7):1147-56.
Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454(7207):961-7.
Kokabu S, Lowery JW, Jimi E. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells. Stem Cells Int. 2016;2016:3753581.
Subash-Babu P, Alshatwi AA. Ononitol monohydrate enhances PRDM16 & UCP-1 expression, mitochondrial biogenesis and insulin sensitivity via STAT6 and LTB4R in maturing adipocytes. Biomed Pharmacother. 2018;99:375-83.
Mu Q, Fang X, Li X, Zhao D, Mo F, Jiang G, Yu N, Zhang Y, Guo Y, Fu M, Liu JL, Zhang D, Gao S. Ginsenoside Rb1 promotes browning through regulation of PPARgamma in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2015;466(3):530-5.
How to Cite
Authors reatin copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s autorship and initial publication in this journal.