Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (2): 10-19.doi: 10.6040/j.issn.1671-7554.0.2024.0089

• Preclinical Medicine • Previous Articles    

Proteomic analysis of brown adipose tissue in diet-induced obese female mice

LIANG Zhonghao1, ZHUANG Xianghua1,2, HUANG Shan1, HAN Xiaolin1, HUA Mengyu1, JU Liping1,2, CHEN Shihong1,2   

  1. 1. Department of Endocrinology and Metabolism, The Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Multidisciplinary Innovation Center for Nephrology of the Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2024-03-29

PDF (PC)

73

Abstract: Objective To investigate the effects of high-fat diet(HFD)on the proteomics of brown adipose tissue(BAT)in female mice. Methods The obese mice models were established with HFD(HFP group). Mice in the control group were fed with normal diet, while those in the experimental group were fed with HFD. Both groups were fed for 21 weeks and body weight were detected weekly. Body composition was measured with small animal body composition analyzer. The glucose tolerance and insulin tolerance were measured with intraperitoneal glucose tolerance test(IPGTT)and insulin tolerance test(ITT)respectively. After the mice were sacrificed, BAT was quickly collected into liquid nitrogen, and then 4 samples from either group were analyzed with liquid chromatography-tandem mass spectrometry(LC-MS)and proteomics. Results Compared with the control group, the HFD group had significantly increased body weight and fat content, but impaired glucose tolerance and insulin tolerance. Differential proteins were screened with FC>1.5 or <0.67 and P<0.05. Cluster heatmap revealed an increased Ucp1 level in HFD mice, and Western blotting further confirmed higher Ucp1 expression in HFD mice. Subcellular localization analysis indicated that mitochondria were the organelles containing the largest number of differential proteins. Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that the down-regulated proteins in the HFD group were mainly involved with muscle contraction and calcium signaling pathway, while the up-regulated proteins with lipid catabolism, lipid oxidation process, thermogenesis, oxidative phosphorylation and other pathways. Protein interaction analysis suggested that the central proteins of the network were associated with lipid synthesis and fatty acid β oxidation. Conclusion The thermogenic pathway of BAT was enhanced in obese female mice, accompanied with increased oxidation of fatty acid β and decreased fat synthesis.

Key words: Diet-induced obesity, Brown adipose tissue, Thermogenesis, Proteomics

CLC Number: 

  • R589.2
[1] GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years[J]. N Engl J Med, 2017, 377(1): 13-27.
[2] Lin X, Li H. Obesity: epidemiology, pathophysiology, and therapeutics[J]. Front Endocrinol(Lausanne), 2021, 12: 706978. doi: 10.3389/fendo.2021.706978.
[3] Martin SS, Aday AW, Almarzooq ZI, et al. 2024 Heart disease andstroke statistics: A Report of US and Global Data From the American Heart Association[J]. Circulation, 2024. doi: 10.1161/CIR.0000000000001209.
[4] 张淑洁, 何云, 张思奇, 等. 肥胖高血压患者血压变异性的研究进展[J]. 中华高血压杂志, 2020, 28(6): 580-586.
[5] Ronald CK, Guoxiao W, Kevin YL. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome[J]. J Clin Invest, 2019, 129(10): 3990-4000.
[6] Ong FJ, Ahmed BA, Oreskovich SM, et al. Recent advances in the detection of brown adipose tissue in adult humans: a review[J]. Clin Sci(Lond), 2018, 132(10): 1039-1054.
[7] Jurado-Fasoli L, Sanchez-Delgado G, Alcantara JMA, et al. Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts[J]. EBioMedicine, 2024,100: 104948. doi:10.1016/j.ebiom.2023.104968.
[8] Brahmbhatt P, Ataei F, Parent EE, et al. Atypically intense pharmacologically induced brown fat activation on FDG PET/CT[J]. Clin Nucl Med, 2023, 48(3): 233-236.
[9] Cani PD, Van Hul M. Gut microbiota in overweight and obesity: crosstalk with adipose tissue[J]. Nat Rev Gastroenterol Hepatol, 2023. doi: 10.1038/s41575-023-00867-z.
[10] Ikeda K, Kang Q, Yoneshiro T, et al. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis[J]. Nat Med, 2017, 23(12): 1454-1465.
[11] Kazak L, Chouchani ET, Jedrychowski MP, et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat[J]. Cell, 2015, 163(3): 643-655.
[12] Gómez-García I, Trepiana J, Fernández-Quintela A, et al. Sexual dimorphism in brown adipose tissue activation and white adipose tissue browning[J]. Int J Mol Sci, 2022, 23(15): 8250. doi: 10.3390/ijms23158250.
[13] Patel S, Sparman NZR, Arneson D, et al. Mammary duct luminal epithelium controls adipocyte thermogenic programme[J]. Nature, 2023, 620(7972): 192-199.
[14] Mauvais-Jarvis F. Sex differences in energy metabolism: Natural selection, mechanisms and consequences[J]. Nat Rev Nephrol, 2024, 20(1): 56-69.
[15] Maric I, Krieger JP, van der Velden P, et al. Sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents[J]. Front Nutr, 2022, 9: 828522. doi: 10.3389/fnut.2022.828522.
[16] Wang C, Jiang S, Cheng J, et al. Deciphering the difference of casein fraction in human milk associated with infant gender using quantitative proteomics[J]. Int J Biol Macromol, 2023, 247: 125796. doi: 10.1016/j.ijbiomac.2023.125796.
[17] 李雁儒, 李娟, 李培龙, 等. 胰腺癌不同进展期血清外泌体蛋白组学分析[J]. 山东大学学报(医学版), 2022, 60(10): 33-41. LI Yanru, LI Juan, LI Peilong, et al. Proteomic analysis of serum exosomes in pancreatic cancer withdifferent stages of progress[J]. Journal of Shandong University(Health Sciences), 2022, 60(10): 33-41.
[18] Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch[J]. Nature, 2008, 454(7207): 961-967.
[19] Li F, Jing J, Movahed M, et al. Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat[J]. Nat Commun, 2021, 12(1): 6838. doi: 10.1038/s41467-021-27141-7.
[20] Kyriazis ID, Vassi E, Alvanou M, et al. The impact of diet upon mitochondrial physiology[J]. Int J Mol Med, 2022, 50(5): 135.
[21] Takeda Y, Harada Y, Yoshikawa T, et al. Mitochondrial energy metabolism in the regulation of thermogenic brown fats and human metabolic diseases[J]. Int J Mol Sci, 2023, 24(2): 1352. doi: 10.3390/ijms24021352.
[22] Jingyi C, Qi Z, Lin L, et al. Global transcriptome analysis of brown adipose tissue of diet-induced obese mice[J]. Int J Mol Sci, 2018, 19(4): 1095. doi: 10.3390/ijms19041095.
[23] Kim HS, Ryoo ZY, Choi SU, et al. Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues[J]. Gene, 2015, 565(1): 15-21.
[24] Schmid GM, Converset V, Walter N, et al. Effect of highct o diet on the expression of proteins in muscle, adipose tissues, and liver of C57BL/6 mice[J]. Proteomics, 2004, 4(8): 2270-2282.
[25] Rosen ED, Spiegelman BM. What we talk about when we talk about fat[J]. Cell, 2014, 156(1-2): 20-44.
[26] Schlaepfer IR, Joshi M. CPT1A-mediated fat oxidation, mechanisms, and therapeutic potential[J]. Endocrinology, 2020, 161(2): bqz046. doi: 10.1210/endocr/bqz046.
[27] Tonazzi A, Giangregorio N, Console L, et al. The mitochondrial carnitine acyl-carnitine carrier(SLC25A20): molecular mechanisms of transport, role in redox sensing and interaction with drugs[J]. Biomolecules, 2021, 11(4): 521. doi: 10.3390/biom11040521.
[28] Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets[J]. Nat Rev Drug Discov, 2008, 7(6): 489-503.
[29] Gallardo-Montejano VI, Yang C, Hahner L, et al. Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance[J]. Nat Commun, 2021, 12(1): 3320. doi: 10.1038/s41467-021-23601-2.
[30] Sanchez-Gurmaches J, Tang Y, Jespersen NZ, et al. Brown fat AKT2 is a cold-induced kinase that stimulates ChREBP-mediated de novo lipogenesis to optimize fuel storage and thermogenesis[J]. Cell Metab, 2018, 27(1): 195-209.e6.
[31] Da Eira D, Jani S, Stefanovic M, et al. The ketogenic diet promotes triacylglycerol recycling in white adipose tissue and uncoupled fat oxidation in brown adipose tissue, but does not reduce adiposity in rats[J]. J Nutr Biochem, 2023, 120: 109412. doi: 10.1016/j.jnutbio.2023.109412.
[32] von Essen G, Lindsund E, Maldonado EM, et al. Highly recruited brown adipose tissue does not in itself protect against obesity[J]. Mol Metab, 2023, 76: 101782. doi: 10.1016/j.molmet.2023.101782.
[1] LI Yanru, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Proteomic analysis of serum exosomes in pancreatic cancer with different stages of progress [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 33-41.
[2] CHEN Lixiao, YING Xinjiang, CHEN Xinwei, WANG Fei, SUN Zhenfeng, DONG Pin. Identification of proteins in hypopharyngeal squamous cell carcinoma by mass spectrometry and screening of prognostic target molecules [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 140-147.
[3] LIU Yafei, ZHANG Qishu, YUAN Shoudao, Jason J. Chen. Mass spectrometry analysis of differentially expressed proteins between HPV immortalized cell line and SiHa cell line [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 22-26.
[4] WANG Xiaoyue, WANG Daoguang, GUO Jisheng, LI Cuiling, JING Ruirui, LÜ Xin, CHEN Xinjun, YANG Jinghua. Label-free quantification of proteomic changes in ethanol-induced hepatocyte [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 12-16.
[5] YUAN Shoudao, WANG Fengqin, ZHANG Jiao, ZHAO Weiming, Jason J. Chen. Mass spectrometry analysis of proteins differentially expressed between adenocarcinoma and squamous carcinoma of the cervix [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(8): 14-21.
[6] ZHU Xiaoli1, GUO Shuling1, SU Lei1, FENG Yuxin2, YUAN Fangshu1. Extraction of total proteins from demodex and qualification of their molecular weights [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(5): 58-62.
[7] ZHONG Kaize, ZHAO Jian, YUAN Shoudao, WANG Luyu, JING Yanjie, HAO Tong, CHEN Jianxing, ZHAN Qimin, JIANG Wei, ZHU Changjun, PAN Lina. Centrosome isolation and analysis by mass spectrometry-based proteomics [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(12): 54-59.
[8] ZHANG Huan-li1, CUI Ya-zhou2, ZHOU Xiao-yan2, SHANG Wei1. Comparative proteomic study of epileptic foci in  patients with epilepsy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 80-84.
[9] WANG Hai-bin, MA Wei-ming, XIAO Pan, MA Tian-jia, ZHANG Huai-qiang. Differential  expressions of HSP60 in docetaxel treatment on
advanced hormone-resistant prostate cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(8): 46-50.
[10] XIAO Pan1, ZHANG Huai-qiang1, CUI Ya-zhou2, ZHAO Sheng-tian1, MA Tian-jia1, ZHOU Chun-wen1. A proteomics study of docetaxel-induced apoptosis in
prostate cancer PC3 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(10): 77-.
[11] ZHAN Yu-quan, LI Ming-long, CHEN Hai-yan. Effects of long-term high-protein diet on expressions of IRS2 and GLUT2 in the liver of dietinduced obese rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(6): 1-4.
[12] . Evaluation of androgendependent and androgenindependent 
proteome in LNCaP cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(9): 62-65.
[13] . Metastases associated with proteins in breast cancer by proteomics [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(7): 61-64.
[14] . Comparison of different sample preparation methods for human serum 2DE [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(11): 89-94.
[15] HAN Ming-yong,LIU Qi,YU Jie-kai,ZHENG Shu . Classification and diagnostic prediction of lung cancer using protein profiling of serum and bioinformatics [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(6): 604-607.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd