Abstract
Objective:
To investigate the impact of peroxisome proliferator-activated receptor α deficiency on gene expression of adipose triglyceride lipase and the glycerol transporter aquaglyceroporin 7 in white adipose tissue in the fed and fasted states in relation to glycerol release by isolated adipocytes.
Measurements:
Studies using wild-type and peroxisome proliferator-activated receptor α null mice. Hormone and metabolite concentrations, real-time polymerase chain reaction (PCR), basal and stimulated adipocyte lipolysis, estimated by glycerol release.
Results:
Peroxisome proliferator-activated receptor α deficiency blocked the increase in aquaglyceroporin 7 transcript level and attenuated the increase in adipose triglyceride lipase transcript level in white adipose tissue elicited by fasting. Fasting glycerol levels were lower in peroxisome proliferator-activated receptor α null than wild-type mice, despite increased mobilization of adipocyte fat reserves in vivo as indicated by reduced adipose tissue masses (three distinct depots) and a significantly lower epididymal adipocyte diameter. Basal net glycerol release was unchanged but β-adrenergic-stimulated net glycerol release was higher with isolated adipocytes from fasted peroxisome proliferator-activated receptor α null mice compared with those of fasted wild-type mice.
Conclusion:
Peroxisome proliferator-activated receptor α deficiency prevents effects of fasting to increase adipocyte aquaglyceroporin 7 gene expression, and influences the regulation of inter-tissue glycerol flux after fasting via lowered adipocyte aquaglyceroporin 7 expression. Lowered gene expression of adipose triglyceride lipase and aquaglyceroporin 7 in peroxisome proliferator-activated receptor α null mice is not limiting for adipose triglyceride breakdown in vivo during fasting.
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References
Frayn KN . Adipose tissue as a buffer for daily lipid flux. Diabetologia 2002; 45: 1201–1210.
Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306: 1383–1386.
Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G, Wagner E et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 2002; 277: 4806–4815.
Mulder H, Sorhede-Winzell M, Contreras JA, Fex M, Strom K, Ploug T et al. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact. J Biol Chem 2003; 278: 36380–36388.
Fortier M, Wang SP, Mauriege P, Semache M, Mfuma L, Li H et al. Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. Am J Physiol Endocrinol Metab 2004; 287: E282–E288.
Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS . Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004; 279: 47066–47075.
Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006; 312: 734–737.
Kishida K, Kuriyama H, Funahashi T, Shimomura I, Kihara S, Ouchi N et al. Aquaporin adipose, a putative glycerol channel in adipocytes. J Biol Chem 2000; 275: 20896–20902.
Kishida K, Shimomura I, Kondo H, Kuriyama H, Makino Y, Nishizawa H et al. Genomic structure and insulin-mediated repression of the aquaporin adipose (AQPap), adipose-specific glycerol channel. J Biol Chem 2001; 276: 36251–36260.
Maeda N, Funahashi T, Hibuse T, Nagasawa A, Kishida K, Kuriyama H et al. Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue. Proc Natl Acad Sci USA 2004; 101: 17801–17806.
Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S et al. Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 2005; 280: 15493–15496.
Hibuse T, Maeda N, Funahashi T, Yamamoto K, Nagasawa A, Mizunoya W et al. Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci USA 2005; 102: 10993–10998.
Knauf C, Rieusset J, Foretz M, Cani PD, Uldry M, Hosokawa M et al. PPAR{alpha} null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass. role in liver and brain. Endocrinology 2006; 147: 4067–4078.
Patsouris D, Mandard S, Voshol PJ, Escher P, Tan NS, Havekes LM et al. PPARalpha governs glycerol metabolism. J Clin Invest 2004; 114: 94–103.
Rodbell M . Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964; 239: 375–380.
Fryer LG, Holness MJ, Sugden MC . Selective modification of insulin action in adipose tissue by hyperthyroidism. J Endocrinol 1997; 154: 513–522.
Sugden MC, Bulmer K, Gibbons GF, Knight BL, Holness MJ . Peroxisome-proliferator activated receptor (PPAR) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin. Biochem J 2002; 364: 361–368.
Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W . Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 1999; 103: 1489–1498.
Islam KK, Knight BL, Frayn KN, Patel DD, Gibbons GF . Deficiency of PPARalpha disturbs the response of lipogenic flux and of lipogenic and cholesterogenic gene expression to dietary cholesterol in mouse white adipose tissue. Biochim Biophys Acta 2005; 1734: 259–268.
Lemberger T, Staels B, Saladin R, Desvergne B, Auwerx J, Wahli W . Regulation of the peroxisome proliferator-activated receptor alpha gene by glucocorticoids. J Biol Chem 1994; 269: 24527–24530.
Guan HP, Li Y, Jensen MV, Newgard CB, Steppan CM, Lazar MA . A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat Med 2002; 8: 1122–1128.
Kuriyama H, Shimomura I, Kishida K, Kondo H, Furuyama N, Nishizawa H et al. Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes 2002; 51: 2915–2921.
Kondo H, Shimomura I, Kishida K, Kuriyama H, Makino Y, Nishizawa H et al. Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation. Eur J Biochem 2002; 269: 1814–1826.
Baba H, Zhang XJ, Wolfe RR . Glycerol gluconeogenesis in fasting humans. Nutrition 1995; 11: 149–153.
Peroni O, Large V, Beylot M . Measuring gluconeogenesis with [2-13C]glycerol and mass isotopomer distribution analysis of glucose. Am J Physiol Endocrinol Metab 1995; 269: E516–E523.
Sjarif DR, Ploos van Amstel JK, Duran M, Beemer FA, Poll-The BT . Isolated and contiguous glycerol kinase gene disorders: a review. J Inherit Metab Dis 2000; 23: 529–547.
Acknowledgements
We are grateful to Diabetes UK (BDA:RDA04/0002863 and BDA:RD03/0002725) for financial support.
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Walker, C., Holness, M., Gibbons, G. et al. Fasting-induced increases in aquaporin 7 and adipose triglyceride lipase mRNA expression in adipose tissue are attenuated by peroxisome proliferator-activated receptor α deficiency. Int J Obes 31, 1165–1171 (2007). https://doi.org/10.1038/sj.ijo.0803555
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DOI: https://doi.org/10.1038/sj.ijo.0803555
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