Global Transcriptome Analysis of Brown Adipose Tissue of Diet-Induced Obese Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Apr 13

PMID 29642370

Citations 12

Authors

Jingyi Cao

Qi Zhu

Lin Liu

Bradley J Glazier

Benjamin C Hinkel

Chun Liang

Haifei Shi

Affiliations

Soon will be listed here.

Abstract

Consumption of a high-fat diet (HFD) promotes the development of obesity, a disease resulting from an imbalance between energy intake and energy expenditure. Brown adipose tissue (BAT) has thermogenic capacity that burns calories to produce heat, and it is a potential target for the treatment and prevention of obesity. There is limited information regarding the impact of HFD on the BAT transcriptome. We hypothesized that HFD-induced obesity would lead to transcriptional regulation of BAT genes. RNA sequencing was used to generate global transcriptome profiles from BAT of lean mice fed with a low-fat diet (LFD) and obese mice fed with a HFD. Gene Ontology (GO) analysis identified increased expression of genes involved in biological processes (BP) related to immune responses, which enhanced molecular function (MF) in chemokine activity; decreased expression of genes involved in BP related to ion transport and muscle structure development, which reduced MF in channel and transporter activity and structural binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathway analysis indicated that pathways associated with innate immunity were enhanced by HFD, while pathways associated with muscle contraction and calcium signaling were suppressed by HFD. Collectively, these results suggest that diet-induced obesity changes transcriptomic signatures of BAT, leading to dysfunction involving inflammation, calcium signaling, ion transport, and cell structural development.

Citing Articles

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies.

Acharjee A, Wijesinghe S, Russ D, Gkoutos G, Jones S J Transl Med. 2024; 22(1):592.

PMID: 38918843 PMC: 11197204. DOI: 10.1186/s12967-024-05414-1.

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences.

Peral-Sanchez I, Hojeij B, Ojeda D, Steegers-Theunissen R, Willaime-Morawek S Genes (Basel). 2022; 13(1).

PMID: 35052371 PMC: 8774448. DOI: 10.3390/genes13010031.

ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.

Sebag S, Zhang Z, Qian Q, Li M, Zhu Z, Harata M Cell Rep. 2021; 37(7):110003.

PMID: 34788615 PMC: 8640996. DOI: 10.1016/j.celrep.2021.110003.

Cecal Ligation and Puncture-Induced Sepsis Promotes Brown Adipose Tissue Inflammation Without Any Impact on Expression of Thermogenic-Related Genes.

Moreno-Navarrete J, Comas F, de Jager V, Fernandez-Real J, Bouma H Front Physiol. 2021; 12:692618.

PMID: 34322037 PMC: 8313297. DOI: 10.3389/fphys.2021.692618.

Involvement of plasminogen activator inhibitor-1 and its related molecules in atrial fibrosis in patients with atrial fibrillation.

Li Q, Lai Y, Gao X, Li X, Deng C, Guo H PeerJ. 2021; 9:e11488.

PMID: 34141473 PMC: 8179226. DOI: 10.7717/peerj.11488.

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

Herrero L, Shapiro H, Nayer A, Lee J, Shoelson S . Inflammation and adipose tissue macrophages in lipodystrophic mice. Proc Natl Acad Sci U S A. 2009; 107(1):240-5. PMC: 2806777. DOI: 10.1073/pnas.0905310107. View

Cypess A, Kahn C . Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes. 2010; 17(2):143-9. PMC: 3593105. DOI: 10.1097/MED.0b013e328337a81f. View

Anderson E, Gutierrez D, Hasty A . Adipose tissue recruitment of leukocytes. Curr Opin Lipidol. 2010; 21(3):172-7. PMC: 3381420. DOI: 10.1097/MOL.0b013e3283393867. View

Gao M, Ma Y, Liu D . High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice. PLoS One. 2015; 10(3):e0119784. PMC: 4358885. DOI: 10.1371/journal.pone.0119784. View

French S, Story M, Jeffery R . Environmental influences on eating and physical activity. Annu Rev Public Health. 2001; 22:309-35. DOI: 10.1146/annurev.publhealth.22.1.309. View

Oh D, Morinaga H, Talukdar S, Bae E, Olefsky J . Increased macrophage migration into adipose tissue in obese mice. Diabetes. 2011; 61(2):346-54. PMC: 3266418. DOI: 10.2337/db11-0860. View

Bystry R, Aluvihare V, Welch K, Kallikourdis M, Betz A . B cells and professional APCs recruit regulatory T cells via CCL4. Nat Immunol. 2001; 2(12):1126-32. DOI: 10.1038/ni735. View

van Marken Lichtenbelt W, Vanhommerig J, Smulders N, Drossaerts J, Kemerink G, Bouvy N . Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009; 360(15):1500-8. DOI: 10.1056/NEJMoa0808718. View

10.

Park S, Ahmad F, Philp A, Baar K, Williams T, Luo H . Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012; 148(3):421-33. PMC: 3431801. DOI: 10.1016/j.cell.2012.01.017. View

11.

Ferrante Jr A . Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med. 2007; 262(4):408-14. DOI: 10.1111/j.1365-2796.2007.01852.x. View

12.

Li B, Dewey C . RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011; 12:323. PMC: 3163565. DOI: 10.1186/1471-2105-12-323. View

13.

Quintens R, Singh S, Lemaire K, De Bock K, Granvik M, Schraenen A . Mice deficient in the respiratory chain gene Cox6a2 are protected against high-fat diet-induced obesity and insulin resistance. PLoS One. 2013; 8(2):e56719. PMC: 3584060. DOI: 10.1371/journal.pone.0056719. View

14.

Tanaka M, Yasuoka A, Shimizu M, Saito Y, Kumakura K, Asakura T . Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats. Genes Nutr. 2017; 12:10. PMC: 5385083. DOI: 10.1186/s12263-017-0558-2. View

15.

Kim H, Ryoo Z, Choi S, Lee S . Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues. Gene. 2015; 565(1):15-21. DOI: 10.1016/j.gene.2015.03.077. View

16.

Gupta R, Rosen E, Spiegelman B . Identifying novel transcriptional components controlling energy metabolism. Cell Metab. 2011; 14(6):739-45. PMC: 3240865. DOI: 10.1016/j.cmet.2011.11.007. View

17.

Cypess A, Lehman S, Williams G, Tal I, Rodman D, Goldfine A . Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009; 360(15):1509-17. PMC: 2859951. DOI: 10.1056/NEJMoa0810780. View

18.

Siersbaek M, Varticovski L, Yang S, Baek S, Nielsen R, Mandrup S . High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss. Sci Rep. 2017; 7:40220. PMC: 5223143. DOI: 10.1038/srep40220. View

19.

Schulz T, Tseng Y . Brown adipose tissue: development, metabolism and beyond. Biochem J. 2013; 453(2):167-78. PMC: 3887508. DOI: 10.1042/BJ20130457. View

20.

Bal N, Maurya S, Sopariwala D, Sahoo S, Gupta S, Shaikh S . Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med. 2012; 18(10):1575-9. PMC: 3676351. DOI: 10.1038/nm.2897. View