Glycerol Kinase Stimulates Uncoupling Protein 1 Expression by Regulating Fatty Acid Metabolism in Beige Adipocytes

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2020 Apr 11

PMID 32273338

Citations 11

Authors

Mari Iwase

Soshi Tokiwa

Shigeto Seno

Takako Mukai

Yu-Sheng Yeh

Haruya Takahashi

Wataru Nomura

Huei-Fen Jheng

Sigenobu Matsumura

Tatsuya Kusudo

Naoki Osato

Hideo Matsuda

Kazuo Inoue

Teruo Kawada

Tsuyoshi Goto

Affiliations

Soon will be listed here.

Abstract

Browning of adipose tissue is induced by specific stimuli such as cold exposure and consists of up-regulation of thermogenesis in white adipose tissue. Recently, it has emerged as an attractive target for managing obesity in humans. Here, we performed a comprehensive analysis to identify genes associated with browning in murine adipose tissue. We focused on glycerol kinase (GYK) because its mRNA expression pattern is highly correlated with that of uncoupling protein 1 (UCP1), which regulates the thermogenic capacity of adipocytes. Cold exposure-induced up-regulation in inguinal white adipose tissue (iWAT) was partially abolished by knockdown (KD) Consistently, the KD inhibited expression induced by treatment with the β-adrenergic receptors (βAR) agonist isoproterenol (Iso) and resulted in impaired uncoupled respiration. KD also suppressed Iso- and adenylate cyclase activator-induced transcriptional activation and phosphorylation of the cAMP response element-binding protein (CREB). However, we did not observe these effects with a cAMP analog. Therefore KD related to Iso-induced cAMP products. In Iso-treated KD adipocytes, stearoyl-CoA desaturase 1 (SCD1) was up-regulated, and monounsaturated fatty acids such as palmitoleic acid (POA) accumulated. Moreover, a SCD1 inhibitor treatment recovered the KD-induced down-regulation and POA treatment down-regulated Iso-activated Our findings suggest that stimulates expression via a mechanism that partially depends on the βAR-cAMP-CREB pathway and -mediated regulation of fatty acid metabolism.

Citing Articles

Structure characterization of Grifola frondosa polysaccharide and its effect on insulin resistance in HFD-fed mice.

Ding Y, Lan J, Wang Y, Pan Y, Song T, Liu S NPJ Sci Food. 2025; 9(1):3.

PMID: 39774946 PMC: 11707143. DOI: 10.1038/s41538-024-00359-7.

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet.

Gao G, Liu R, Hu S, He M, Zhang J, Gao D J Anim Sci Biotechnol. 2024; 15(1):60.

PMID: 38693536 PMC: 11064361. DOI: 10.1186/s40104-024-01016-5.

Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes.

Cetin E, Pedersen B, Porter L, Adler G, Burak M Front Endocrinol (Lausanne). 2024; 14:1306528.

PMID: 38313838 PMC: 10835623. DOI: 10.3389/fendo.2023.1306528.

Hyperphagia of female UCP1-deficient mice blunts anti-obesity effects of FGF21.

Klein Hazebroek M, Laterveer R, Kutschke M, Ramsak Marceta V, Barthem C, Keipert S Sci Rep. 2023; 13(1):10288.

PMID: 37355753 PMC: 10290677. DOI: 10.1038/s41598-023-37264-0.

Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis.

Coulter A, Greenway F, Zhang D, Ghosh S, Coulter C, James S Front Endocrinol (Lausanne). 2023; 14():1148954.

PMID: 37143734 PMC: 10153092. DOI: 10.3389/fendo.2023.1148954.

References

Sharp L, Shinoda K, Ohno H, Scheel D, Tomoda E, Ruiz L . Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS One. 2012; 7(11):e49452. PMC: 3500293. DOI: 10.1371/journal.pone.0049452. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Quinn P, Wong T, Magnuson M, Shabb J, GRANNER D . Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1988; 8(8):3467-75. PMC: 363584. DOI: 10.1128/mcb.8.8.3467-3475.1988. View

Guan H, Li Y, Jensen M, Newgard C, Steppan C, Lazar M . A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat Med. 2002; 8(10):1122-8. DOI: 10.1038/nm780. View

Cannon B, Nedergaard J . Brown adipose tissue: function and physiological significance. Physiol Rev. 2004; 84(1):277-359. DOI: 10.1152/physrev.00015.2003. View

Garcia R, Roemmich J, Claycombe K . Evaluation of markers of beige adipocytes in white adipose tissue of the mouse. Nutr Metab (Lond). 2016; 13:24. PMC: 4797138. DOI: 10.1186/s12986-016-0081-2. View

de Souza C, Vannice G, Rosa Neto J, Calder P . Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?. Mol Nutr Food Res. 2017; 62(1). DOI: 10.1002/mnfr.201700504. View

Souza C, Teixeira A, Lima E, Batatinha H, Gomes L, Carvalho-Silva M . Palmitoleic acid (n-7) attenuates the immunometabolic disturbances caused by a high-fat diet independently of PPARα. Mediators Inflamm. 2014; 2014:582197. PMC: 4131426. DOI: 10.1155/2014/582197. View

Festuccia W, Guerra-Sa R, Kawashita N, Garofalo M, Evangelista E, Rodrigues V . Expression of glycerokinase in brown adipose tissue is stimulated by the sympathetic nervous system. Am J Physiol Regul Integr Comp Physiol. 2003; 284(6):R1536-41. DOI: 10.1152/ajpregu.00764.2002. View

10.

Goto T, Naknukool S, Yoshitake R, Hanafusa Y, Tokiwa S, Li Y . Proinflammatory cytokine interleukin-1β suppresses cold-induced thermogenesis in adipocytes. Cytokine. 2015; 77:107-14. DOI: 10.1016/j.cyto.2015.11.001. View

11.

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

12.

Krauss S, Zhang C, Lowell B . The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol. 2005; 6(3):248-61. DOI: 10.1038/nrm1592. View

13.

Cao H, Gerhold K, Mayers J, Wiest M, Watkins S, Hotamisligil G . Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008; 134(6):933-44. PMC: 2728618. DOI: 10.1016/j.cell.2008.07.048. View

14.

Hunnicutt J, Hardy R, Williford J, McDonald J . Saturated fatty acid-induced insulin resistance in rat adipocytes. Diabetes. 1994; 43(4):540-5. DOI: 10.2337/diab.43.4.540. View

15.

Lasar D, Rosenwald M, Kiehlmann E, Balaz M, Tall B, Opitz L . Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase. Cell Rep. 2018; 22(3):760-773. DOI: 10.1016/j.celrep.2017.12.067. View

16.

Huq A, Lovell R, Ou C, Beaudet A, Craigen W . X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death. Hum Mol Genet. 1997; 6(11):1803-9. DOI: 10.1093/hmg/6.11.1803. View

17.

Orlicky D, Schaack J . Adenovirus transduction of 3T3-L1 cells. J Lipid Res. 2001; 42(3):460-6. View

18.

Lewis B, Harbord M, Keenan R, Carey W, Harrison R, Robertson E . Isolated glycerol kinase deficiency in a neonate. J Child Neurol. 1994; 9(1):70-3. DOI: 10.1177/088307389400900118. View

19.

Kennedy A, Martinez K, Chuang C, LaPoint K, McIntosh M . Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr. 2008; 139(1):1-4. DOI: 10.3945/jn.108.098269. View

20.

Jiang G, Li Z, Liu F, Ellsworth K, Dallas-Yang Q, Wu M . Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J Clin Invest. 2005; 115(4):1030-8. PMC: 1062893. DOI: 10.1172/JCI23962. View