Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Yang,Junpeng; Ren,Jianmin; Song,Jun; Liu,Fuqiang; Wu,Chuanlong; Wang,Xuping; Gong,Lei; Li,Wenjuan; Xiao,Fang; Yan,Fei; Hou,Xinguo; Chen,Li

doi:10.3892/ijmm.2013.1350

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Authors:
- Junpeng Yang
- Jianmin Ren
- Jun Song
- Fuqiang Liu
- Chuanlong Wu
- Xuping Wang
- Lei Gong
- Wenjuan Li
- Fang Xiao
- Fei Yan
- Xinguo Hou
- Li Chen
View Affiliations

Affiliations: Department of Endocrinology of Qilu Hospital and Institute of Endocrinology and Metabolism, Shandong University, Jinan, Shandong, P.R. China, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Qilu Hospital, Jinan, Shandong, P.R. China
Published online on: April 15, 2013 https://doi.org/10.3892/ijmm.2013.1350
Pages: 1429-1435

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance. Adipocyte hyperplasia stimulated by preadipocyte differentiation has a positive effect on adipose tissue insulin sensitivity. However, it remains less clear whether GLP-1 plays a role in adipogenesis. In this study, we examined the effect of GLP-1 on preadipocyte differentiation and investigated the mechanisms that may be involved in this effect. In our 3T3-L1 cell study, we tested the levels of adipocyte-specific markers and signaling pathways during preadipocyte differentiation. In addition, Oil Red O staining was used to examine lipid accumulation. Image Pro Plus 5.02 was used to analyze the size and number of lipid droplets. We found that GLP-1 elevated the protein expression levels of free fatty acid-binding protein 4 (aP2) and the transcription factor peroxisome proliferator-activated receptor-γ (PPAR‑γ) in a dose-dependent manner during 3T3‑L1 preadipocyte differentiation. Furthermore, RT‑PCR results showed that GLP-1 promoted CCAAT/enhancer-binding protein α (C/EBPα) and lipoprotein lipase (LPL) expression at the transcriptional level. These data suggest that GLP-1 promotes preadipocyte differentiation. Our study also found that treatment of the cells with 100 nM GLP-1 enhanced the phosphorylation of Akt signaling during the first 24 h of differentiation. Although Oil Red O staining showed that GLP‑1 had no significant effect on lipid accumulation, there were increased numbers of small adipocytes in the cells treated with 100 nM GLP‑1. Taken together, these results indicate that GLP-1 regulates 3T3‑L1 adipogenesis and the Akt signaling pathway may be involved in this process. The differentiated small adipocytes may have a positive effect against insulin resistance and obesity.

View Figures

View References

1	Hossain P, Kawar B and El Nahas M: Obesity and diabetes in the developing world - a growing challenge. N Engl J Med. 356:213–215. 2007. View Article : Google Scholar : PubMed/NCBI
2	Shi H, Akunuru S, Bierman JC, et al: Diet-induced obese mice are leptin insufficient after weight reduction. Obesity. 17:1702–1709. 2009. View Article : Google Scholar : PubMed/NCBI
3	Seale P and Lazar MA: Brown fat in humans: turning up the heat on obesity. Diabetes. 58:1482–1484. 2009. View Article : Google Scholar : PubMed/NCBI
4	Dahlman I and Arner P: Obesity and polymorphisms in genes regulating human adipose tissue. Int J Obes. 31:1629–1641. 2007. View Article : Google Scholar : PubMed/NCBI
5	Sun K, Kusminski CM and Scherer PE: Adipose tissue remodeling and obesity. J Clin Invest. 121:2094–2101. 2011. View Article : Google Scholar : PubMed/NCBI
6	Cristancho AG and Lazar MA: Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 12:722–734. 2011. View Article : Google Scholar : PubMed/NCBI
7	Spalding KL, Arner E, Westermark PO, et al: Dynamics of fat cell turnover in humans. Nature. 453:783–787. 2008. View Article : Google Scholar : PubMed/NCBI
8	Tchoukalova YD, Votruba SB, Tchkonia T, et al: Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci USA. 107:18226–18231. 2010. View Article : Google Scholar : PubMed/NCBI
9	Hoffstedt J, Arner E, Wahrenberg H, et al: Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia. 53:2496–2503. 2010. View Article : Google Scholar : PubMed/NCBI
10	Koenen TB, Tack CJ, Kroese JM, et al: Pioglitazone treatment enlarges subcutaneous adipocytes in insulin-resistant patients. J Clin Endocrinol Metab. 94:4453–4457. 2009. View Article : Google Scholar : PubMed/NCBI
11	Veilleux A, Caron-Jobin M, Noel S, et al: Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes. 60:1504–1511. 2011. View Article : Google Scholar : PubMed/NCBI
12	Meier JJ: GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 8:728–742. 2012. View Article : Google Scholar : PubMed/NCBI
13	Kielgast U, Holst JJ and Madsbad S: Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function. Diabetes. 60:1599–1607. 2011.PubMed/NCBI
14	Ben-Shlomo S, Zvibel I, Shnell M, et al: Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J Hepatol. 54:1214–1223. 2011. View Article : Google Scholar : PubMed/NCBI
15	Chai W, Dong Z, Wang N, et al: Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes. 61:888–896. 2012. View Article : Google Scholar : PubMed/NCBI
16	Gao H, Wang X, Zhang Z, et al: GLP-1 amplifies insulin signaling by up-regulation of IRβ, IRS-1 and Glut4 in 3T3-L1 adipocytes. Endocrine. 32:90–95. 2007.PubMed/NCBI
17	Lee YS, Park MS, Choung JS, et al: Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes. Diabetologia. 55:2456–2468. 2012. View Article : Google Scholar : PubMed/NCBI
18	He M, Su H, Gao W, et al: Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice. PLoS One. 5:e142052010. View Article : Google Scholar : PubMed/NCBI
19	Bass J and Takahashi JS: Circadian integration of metabolism and energetics. Science. 330:1349–1354. 2010. View Article : Google Scholar : PubMed/NCBI
20	Cristancho AG and Lazar MA: Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 12:722–734. 2011. View Article : Google Scholar : PubMed/NCBI
21	Kim GS, Park HJ, Woo JH, et al: Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells. BMC Complement Altern Med. 12:312012. View Article : Google Scholar : PubMed/NCBI
22	Choi SS, Cha BY, Iida K, et al: Honokiol enhances adipocyte differentiation by potentiating insulin signaling in 3T3-L1 preadipocytes. J Nat Med. 65:424–430. 2011. View Article : Google Scholar : PubMed/NCBI
23	Zhang M, Ikeda K, Xu JW, et al: Genistein suppresses adipogenesis of 3T3-L1 cells via multiple signal pathways. Phytother Res. 23:713–718. 2009. View Article : Google Scholar : PubMed/NCBI
24	Fischer-Posovszky P, Tews D, Horenburg S, et al: Differential function of Akt1 and Akt2 in human adipocytes. Mol Cell Endocrinol. 358:135–143. 2012. View Article : Google Scholar : PubMed/NCBI
25	Polvani S, Tarocchi M and Galli A: PPARγ and oxidative stress: Con(β) catenating NRF2 and FOXO. PPAR Res. 2012:6410872012.
26	Dowell P, Otto TC, Adi S and Lane MD: Convergence of peroxisome proliferator-activated receptor γ and foxo1 signaling pathways. J Biol Chem. 278:45485–45491. 2003.
27	Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez Mdel M and Blázquez E: Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow. Am J Physiol Endocrinol Metab. 298:E634–E643. 2010. View Article : Google Scholar : PubMed/NCBI
28	Challa TD, Beaton N, Arnold M, et al: Regulation of adipocyte formation by GLP-1/GLP-1R signaling. J Biol Chem. 287:6421–6430. 2012. View Article : Google Scholar : PubMed/NCBI
29	Kang JG, Park CY, Ihm SH, et al: Mechanisms of adipose tissue redistribution with rosiglitazone treatment in various adipose depots. Metabolism. 59:46–53. 2010. View Article : Google Scholar : PubMed/NCBI
30	Dubuisson O, Dhurandhar EJ, Krishnapuram R, et al: PPARgamma-independent increase in glucose uptake and adiponectin abundance in fat cells. Endocrinology. 152:3648–3660. 2011. View Article : Google Scholar : PubMed/NCBI
31	Chang YC and Cho HJ: Ascofuranone stimulates expression of adiponectin and peroxisome proliferator activated receptor through the modulation of mitogen activated protein kinase family members in 3T3-L1, murine pre-adipocyte cell line. Biochem Biophys Res Commun. 422:423–428. 2012. View Article : Google Scholar