Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue.
3T3-L1 Cells
Adipocytes
/ metabolism
Adipose Tissue
/ metabolism
Animals
Catecholamines
/ pharmacology
Culture Media
/ chemistry
Fatty Acids
/ metabolism
Glucose
/ metabolism
Glycerol
/ metabolism
Glycerophosphates
/ biosynthesis
Isoproterenol
/ pharmacology
Lipase
/ metabolism
Lipolysis
/ drug effects
Male
Mice
Rats
Rats, Wistar
Signal Transduction
/ drug effects
Triglycerides
/ metabolism
Fat
Glucose uptake
Glycerol
Isoproterenol
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
05
03
2021
accepted:
02
08
2021
pubmed:
11
8
2021
medline:
29
1
2022
entrez:
10
8
2021
Statut:
ppublish
Résumé
During lipolysis, triglyceride (TG) are hydrolyzed into a glycerol and fatty acids in adipocyte. A significant portion of the fatty acids are re-esterificated into TG, and this is a critical step in promoting lipolysis. Although glycerol-3-phosphate (G3P) is required for triglyceride synthesis in mammalian cell, the substrate for G3P synthesis during active lipolysis is not known. A recent study showed that the inhibition of glucose uptake reduces catecholamine-stimulated lipolysis, suggesting that glucose availability is important in lipolysis in adipocytes. We hypothesized that glucose might play an essential role in generating G3P and thereby promoting catecholamine-stimulated lipolysis in adipocytes. Therefore, we determined the effect of glucose availability on catecholamine-stimulated lipolysis in 3T3-L1 adipocytes and rat adipose tissue. 3T3-L1 adipocytes and rat epididymal fat pads were cultured in a medium with/without glucose during stimulation by isoproterenol. Glycerol release was higher when adipocytes were cultured in a glucose-containing medium than that in a medium without glucose. Measurement of glucose uptake during catecholamine-stimulated lipolysis showed a slight, but significant increase in glucose uptake. We also compared glucose metabolism-related protein, such as glucose transporter 4, hexokinase, glycerol-3-phosphate dehydrogenase and lipase contents between fat tissues that play a critical role in active lipolysis. Epididymal fat exhibited higher lipolytic activity than inguinal fat because of higher lipase and glucose metabolism-related protein contents. We demonstrated that catecholamine-stimulated lipolysis is enhanced in the presence of glucose, and suggests that glucose is one of the primary substrates for G3P in adipocytes during active lipolysis.
Sections du résumé
BACKGROUND
BACKGROUND
During lipolysis, triglyceride (TG) are hydrolyzed into a glycerol and fatty acids in adipocyte. A significant portion of the fatty acids are re-esterificated into TG, and this is a critical step in promoting lipolysis. Although glycerol-3-phosphate (G3P) is required for triglyceride synthesis in mammalian cell, the substrate for G3P synthesis during active lipolysis is not known. A recent study showed that the inhibition of glucose uptake reduces catecholamine-stimulated lipolysis, suggesting that glucose availability is important in lipolysis in adipocytes. We hypothesized that glucose might play an essential role in generating G3P and thereby promoting catecholamine-stimulated lipolysis in adipocytes. Therefore, we determined the effect of glucose availability on catecholamine-stimulated lipolysis in 3T3-L1 adipocytes and rat adipose tissue.
METHODS AND RESULTS
RESULTS
3T3-L1 adipocytes and rat epididymal fat pads were cultured in a medium with/without glucose during stimulation by isoproterenol. Glycerol release was higher when adipocytes were cultured in a glucose-containing medium than that in a medium without glucose. Measurement of glucose uptake during catecholamine-stimulated lipolysis showed a slight, but significant increase in glucose uptake. We also compared glucose metabolism-related protein, such as glucose transporter 4, hexokinase, glycerol-3-phosphate dehydrogenase and lipase contents between fat tissues that play a critical role in active lipolysis. Epididymal fat exhibited higher lipolytic activity than inguinal fat because of higher lipase and glucose metabolism-related protein contents.
CONCLUSION
CONCLUSIONS
We demonstrated that catecholamine-stimulated lipolysis is enhanced in the presence of glucose, and suggests that glucose is one of the primary substrates for G3P in adipocytes during active lipolysis.
Identifiants
pubmed: 34374898
doi: 10.1007/s11033-021-06617-1
pii: 10.1007/s11033-021-06617-1
doi:
Substances chimiques
Catecholamines
0
Culture Media
0
Fatty Acids
0
Glycerophosphates
0
Triglycerides
0
alpha-glycerophosphoric acid
9NTI6P3O4X
Lipase
EC 3.1.1.3
Glucose
IY9XDZ35W2
Isoproterenol
L628TT009W
Glycerol
PDC6A3C0OX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6269-6276Subventions
Organisme : Japan Society for the Promotion of Science
ID : 20K11364
Organisme : Japan Society for the Promotion of Science
ID : 19K11553
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Robinson J, Newsholme EA (1967) Glycerol kinase activities in rat heart and adipose tissue. Biochem J 104(1):2C-4C. https://doi.org/10.1042/bj1040002c
doi: 10.1042/bj1040002c
pubmed: 6035520
pmcid: 1270581
Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27:79–101. https://doi.org/10.1146/annurev.nutr.27.061406.093734
doi: 10.1146/annurev.nutr.27.061406.093734
pubmed: 17313320
pmcid: 2885771
Nye C, Kim J, Kalhan SC, Hanson RW (2008) Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol Metab 19(10):356–361. https://doi.org/10.1016/j.tem.2008.08.003
doi: 10.1016/j.tem.2008.08.003
pubmed: 18929494
Edens NK, Leibel RL, Hirsch J (1990) Mechanism of free fatty acid re-esterification in human adipocytes in vitro. J Lipid Res 31(8):1423–1431
doi: 10.1016/S0022-2275(20)42613-6
Hashimoto T, Segawa H, Okuno M, Kano H, Hamaguchi HO, Haraguchi T et al (2012) Active involvement of micro-lipid droplets and lipid-droplet-associated proteins in hormone-stimulated lipolysis in adipocytes. J Cell Sci 125(Pt 24):6127–6136. https://doi.org/10.1242/jcs.113084
doi: 10.1242/jcs.113084
pubmed: 23108672
Viswanadha S, Londos C (2006) Optimized conditions for measuring lipolysis in murine primary adipocytes. J Lipid Res 47(8):1859–1864. https://doi.org/10.1194/jlr.D600005-JLR200
doi: 10.1194/jlr.D600005-JLR200
pubmed: 16675855
Morimoto C, Tsujita T, Okuda H (1997) Norepinephrine-induced lipolysis in rat fat cells from visceral and subcutaneous sites: role of hormone-sensitive lipase and lipid droplets. J Lipid Res 38(1):132–138
doi: 10.1016/S0022-2275(20)37282-5
Laplante M, Festuccia WT, Soucy G, Gélinas Y, Lalonde J, Berger JP et al (2006) Mechanisms of the depot specificity of peroxisome proliferator-activated receptor gamma action on adipose tissue metabolism. Diabetes 55(10):2771–2778. https://doi.org/10.2337/db06-0551
doi: 10.2337/db06-0551
pubmed: 17003342
Kelly KL, Mato JM, Merida I, Jarett L (1987) Glucose transport and antilipolysis are differentially regulated by the polar head group of an insulin-sensitive glycophospholipid. Proc Natl Acad Sci U S A 84(18):6404–6407. https://doi.org/10.1073/pnas.84.18.6404
doi: 10.1073/pnas.84.18.6404
pubmed: 3306676
pmcid: 299084
Higashida K, Takeuchi N, Inoue S, Hashimoto T, Nakai N (2020) Iron deficiency attenuates catecholamine-stimulated lipolysis via downregulation of lipolysis-related proteins and glucose utilization in 3T3-L1 adipocytes. Mol Med Rep 21(3):1383–1389. https://doi.org/10.3892/mmr.2020.10929
doi: 10.3892/mmr.2020.10929
pubmed: 32016466
Welinder C, Ekblad L (2011) Coomassie staining as loading control in Western blot analysis. J Proteome Res 10(3):1416–1419. https://doi.org/10.1021/pr1011476
doi: 10.1021/pr1011476
pubmed: 21186791
Ueyama A, Sato T, Yoshida H, Magata K, Koga N (2000) Nonradioisotope assay of glucose uptake activity in rat skeletal muscle using enzymatic measurement of 2-deoxyglucose 6-phosphate in vitro and in vivo. Biol Signals Recept 9(5):267–274. https://doi.org/10.1159/000014649
doi: 10.1159/000014649
pubmed: 10965062
Ballard FJ, Hanson RW, Leveille GA (1967) Phosphoenolpyruvate carboxykinase and the synthesis of glyceride-glycerol from pyruvate in adipose tissue. J Biol Chem 242(11):2746–2750
doi: 10.1016/S0021-9258(18)99631-6
Reshef L, Niv J, Shapiro B (1967) Effect of propionate on pyruvate metabolism in adipose tissue. J Lipid Res 8(6):688–691
doi: 10.1016/S0022-2275(20)38893-3
Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS (2007) Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am J Physiol Gastrointest Liver Physiol 293(1):G1–G4. https://doi.org/10.1152/ajpgi.00554.2006
Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M et al (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science (New York, NY) 306(5700):1383–1386. https://doi.org/10.1126/science.1100747
doi: 10.1126/science.1100747
Hoffstedt J, Arner P, Hellers G, Lönnqvist F (1997) Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. J Lipid Res 38(4):795–804
doi: 10.1016/S0022-2275(20)37246-1
Mullins GR, Wang L, Raje V, Sherwood SG, Grande RC, Boroda S et al (2014) Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes. Proc Natl Acad Sci U S A 111(49):17450–17455. https://doi.org/10.1073/pnas.1410530111
doi: 10.1073/pnas.1410530111
pubmed: 25422441
pmcid: 4267365
Smith U, Kuroda M, Simpson IA (1984) Counter-regulation of insulin-stimulated glucose transport by catecholamines in the isolated rat adipose cell. J Biol Chem 259(14):8758–8763
doi: 10.1016/S0021-9258(17)47218-8
Thorens B, Mueckler M (2010) Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 298(2):E141–E145. https://doi.org/10.1152/ajpendo.00712.2009
doi: 10.1152/ajpendo.00712.2009
pubmed: 20009031
Joost HG, Bell GI, Best JD, Birnbaum MJ, Charron MJ, Chen YT et al (2002) Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. Am J Physiol Endocrinol Metab 282(4):E974–E976. https://doi.org/10.1152/ajpendo.00407.2001
doi: 10.1152/ajpendo.00407.2001
pubmed: 11882521
Mueckler M (1994) Facilitative glucose transporters. Eur J Biochem 219(3):713–725. https://doi.org/10.1111/j.1432-1033.1994.tb18550.x
doi: 10.1111/j.1432-1033.1994.tb18550.x
pubmed: 8112322
Watson RT, Kanzaki M, Pessin JE (2004) Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocr Rev 25(2):177–204. https://doi.org/10.1210/er.2003-0011
doi: 10.1210/er.2003-0011
pubmed: 15082519
Foster LJ, Klip A (2000) Mechanism and regulation of GLUT-4 vesicle fusion in muscle and fat cells. Am J Physiol Cell Physiol 279(4):C877–C890. https://doi.org/10.1152/ajpcell.2000.279.4.C877
doi: 10.1152/ajpcell.2000.279.4.C877
pubmed: 11003568
Clancy BM, Czech MP (1990) Hexose transport stimulation and membrane redistribution of glucose transporter isoforms in response to cholera toxin, dibutyryl cyclic AMP, and insulin in 3T3-L1 adipocytes. J Biol Chem 265(21):12434–12443
doi: 10.1016/S0021-9258(19)38365-6
Beg M, Zhang W, McCourt AC, Enerbäck S (2021) ATGL activity regulates GLUT1-mediated glucose uptake and lactate production via TXNIP stability in adipocytes. J Biol Chem 296:100332. https://doi.org/10.1016/j.jbc.2021.100332
doi: 10.1016/j.jbc.2021.100332
pubmed: 33508319
pmcid: 7949114
Turpin BP, Duckworth WC, Solomon SS (1977) Perifusion of isolated rat adipose cells. Modulation of lipolysis by adenosine. J Clin Invest. 60(2):442–448. https://doi.org/10.1172/jci108794
doi: 10.1172/jci108794
pubmed: 874102
pmcid: 372386