White-to-Beige and Back: Adipocyte Conversion and Transcriptional Reprogramming

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Jun 27

PMID 38931457

Authors

Stanislav Boychenko

Vera S Egorova

Andrew Brovin

Alexander D Egorov

Affiliations

Soon will be listed here.

Abstract

Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced physical activity. Two types of adipose tissue widely known are white and brown. While white adipose tissue functions predominantly as a key energy storage, brown adipose tissue has a greater mass of mitochondria and expresses the uncoupling protein 1 () gene, which allows thermogenesis and rapid catabolism. Even though white and brown adipocytes are of different origin, activation of the brown adipocyte differentiation program in white adipose tissue cells forces them to transdifferentiate into "beige" adipocytes, characterized by thermogenesis and intensive lipolysis. Nowadays, researchers in the field of small molecule medicinal chemistry and gene therapy are making efforts to develop new drugs that effectively overcome insulin resistance and counteract obesity. Here, we discuss various aspects of white-to-beige conversion, adipose tissue catabolic re-activation, and non-shivering thermogenesis.

Citing Articles

Impact of Endocrine Disruptors on the Genitourinary Tract.

Caneparo C, Carignan L, Lonina E, Goulet S, Pellerin F, Chabaud S J Xenobiot. 2024; 14(4):1849-1888.

PMID: 39728407 PMC: 11676856. DOI: 10.3390/jox14040099.

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.

References

Gupta R, Mepani R, Kleiner S, Lo J, Khandekar M, Cohen P . Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab. 2012; 15(2):230-9. PMC: 3366493. DOI: 10.1016/j.cmet.2012.01.010. View

Malogolovkin A, Egorov A, Karabelsky A, Ivanov R, Verkhusha V . Optogenetic technologies in translational cancer research. Biotechnol Adv. 2022; 60:108005. DOI: 10.1016/j.biotechadv.2022.108005. View

Ciolino H, Daschner P, Yeh G . Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res. 1998; 58(24):5707-12. View

Jackson E, Shoemaker R, Larian N, Cassis L . Adipose Tissue as a Site of Toxin Accumulation. Compr Physiol. 2017; 7(4):1085-1135. PMC: 6101675. DOI: 10.1002/cphy.c160038. View

Haynes B, Huyck R, James A, Carter M, Gaafar O, Day M . Isolation, Expansion, and Adipogenic Induction of CD34+CD31+ Endothelial Cells from Human Omental and Subcutaneous Adipose Tissue. J Vis Exp. 2018; (137). PMC: 6126511. DOI: 10.3791/57804. View

Wang Q, Li H, Tajima K, Verkerke A, Taxin Z, Hou Z . Post-translational control of beige fat biogenesis by PRDM16 stabilization. Nature. 2022; 609(7925):151-158. PMC: 9433319. DOI: 10.1038/s41586-022-05067-4. View

Kerley-Hamilton J, Trask H, Ridley C, Dufour E, Ringelberg C, Nurinova N . Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet. Environ Health Perspect. 2012; 120(9):1252-9. PMC: 3440132. DOI: 10.1289/ehp.1205003. View

Stohr O, Tao R, Miao J, Copps K, White M . FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance. Cell Rep. 2021; 34(12):108893. PMC: 8529953. DOI: 10.1016/j.celrep.2021.108893. View

Zhang J, Klemm D, Vinson C, Lane M . Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis. J Biol Chem. 2003; 279(6):4471-8. DOI: 10.1074/jbc.M311327200. View

10.

Gourronc F, Perdew G, Robertson L, Klingelhutz A . PCB126 blocks the thermogenic beiging response of adipocytes. Environ Sci Pollut Res Int. 2019; 27(9):8897-8904. PMC: 7098842. DOI: 10.1007/s11356-019-06663-0. View

11.

Jurado-Fasoli L, Sanchez-Delgado G, Alcantara J, Acosta F, Sanchez-Sanchez R, Labayen I . Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts. EBioMedicine. 2024; 100:104948. PMC: 10808934. DOI: 10.1016/j.ebiom.2023.104948. View

12.

Bhalla D, van Noort V . Molecular Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes. J Mol Evol. 2023; 91(5):628-646. DOI: 10.1007/s00239-023-10124-1. View

13.

Kim A, Yoon B, Park H, Seok J, Choi H, Yu J . Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes. BMB Rep. 2015; 49(2):111-5. PMC: 4915114. DOI: 10.5483/bmbrep.2016.49.2.128. View

14.

Sugiura C, Zheng G, Liu L, Sayama K . Catechins and Caffeine Promote Lipid Metabolism and Heat Production Through the Transformation of Differentiated 3T3-L1 Adipocytes from White to Beige Adipocytes. J Food Sci. 2019; 85(1):192-200. DOI: 10.1111/1750-3841.14811. View

15.

Song Z, Revelo X, Shao W, Tian L, Zeng K, Lei H . Dietary Curcumin Intervention Targets Mouse White Adipose Tissue Inflammation and Brown Adipose Tissue UCP1 Expression. Obesity (Silver Spring). 2018; 26(3):547-558. DOI: 10.1002/oby.22110. View

16.

Kanayama T, Kobayashi N, Mamiya S, Nakanishi T, Nishikawa J . Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway. Mol Pharmacol. 2004; 67(3):766-74. DOI: 10.1124/mol.104.008409. View

17.

Gadupudi G, Gourronc F, Ludewig G, Robertson L, Klingelhutz A . PCB126 inhibits adipogenesis of human preadipocytes. Toxicol In Vitro. 2014; 29(1):132-41. PMC: 4250299. DOI: 10.1016/j.tiv.2014.09.015. View

18.

Zhu Y, Liu W, Qi Z . Adipose tissue browning and thermogenesis under physiologically energetic challenges: a remodelled thermogenic system. J Physiol. 2023; 602(1):23-48. DOI: 10.1113/JP285269. View

19.

Abu-Odeh M, Zhang Y, Reilly S, Ebadat N, Keinan O, Valentine J . FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes. Cell Rep. 2021; 35(13):109331. PMC: 8293281. DOI: 10.1016/j.celrep.2021.109331. View

20.

Liu L, Tao Z, Zheng L, Brooke J, Smith C, Liu D . FoxO1 interacts with transcription factor EB and differentially regulates mitochondrial uncoupling proteins via autophagy in adipocytes. Cell Death Discov. 2016; 2:16066. PMC: 5046220. DOI: 10.1038/cddiscovery.2016.66. View