Ketone Body Utilization is Regulated by Male-specific Factors in Rat Subcutaneous Adipocytes

Abstract

Background: Acetoacetyl-CoA synthetase (AACS) is the enzyme responsible for the utilization of ketone bodies for the synthesis of cholesterol and fatty acids and the gene is highly expressed only in the male subcutaneous white adipose tissue (WAT).

Object: This study is to elucidate how AACS is involved in sex-dependent metabolic differences in adipose tissues. To answer this question, we examined the effect of castration on AACS mRNA expression in rat WAT.

Result: Castration did not affect any changes in the level of serum ketone bodies, but it significantly decreased AACS gene expression in subcutaneous WAT. In contrast, expression of the other ketone body utilizing enzyme, succinyl-CoA: 3-oxoacid CoA-transferase (SCOT), did not change. Moreover, the AACS gene was highly expressed in larger-sized adipocytes obtained from rat subcutaneous WAT, and was up-regulated by testosterone in differentiated adipocytes.

Conclusion: Our results suggest that AACS plays male-specific metabolic roles in the regulation of ketone body-utilization for lipogenesis and that sex-specific ketone body-utilization is restricted in subcutaneous WAT.

Key words

fatty acid synthesis - hormone - ketone body-utilization - white adipose tissue - obesity - castration

References

• 1 Abu-Elheiga L, Brinkley WR, Zhong L, Chirala SS, Woldegiorgis G, Wakil SJ. The subcellular localization of acetyl-CoA carboxylase 2.  Proc Natl Acad Sci USA. 2000;  97 1444-1449
• 2 Bieswal F, Ahn MT, Reusens B, Holvoet P, Raes M, Rees WD, Remacle C. The importance of catch-up growth after early malnutrition for the programming of obesity in male rat.  Obesity. 2006;  14 1330-1343
• 3 Endemann G, Goetz PG, Edmond J, Brunengraber H. Lipogenesis from ketone bodies in the isolated perfused rat liver. Evidence for the cytosolic activation of acetoacetate.  J Biol Chem. 1982;  257 3434-3440
• 4 Fukui T, Ito M, Tomita K. Purification and characterization of acetoacetyl-CoA synthetase from Zoogloea ramigera I-16-M.  Eur J Biochem. 1982;  127 423-428
• 5 Harano Y, Kosugi K, Hyosu T, Uno S, Ichikawa Y, Shigeta Y. Sensitive and simplified method for the differential determination of serum levels of ketone bodies.  Clin Chim Acta. 1983;  134 327-336
• 6 Ito M, Fukui T, Kamokari M, Saito T, Tomita K. Purification and characterization of acetoacetyl-CoA synthetase from rat liver.  Biochim Biophys Acta. 1984;  794 183-193
• 7 Kannel WB, Cupples LA, Ramaswami R, Stokes 3rd J, Kreger BE, Higgins M. Regional obesity and risk of cardiovascular disease; the Framingham Study.  J Clin Epidemiol. 1991;  44 183-190
• 8 Lacasa D, Agli B, Pecquery R, Giudicelli Y. Influence of ovariectomy and regional fat distribution on the membranous transducing system controlling lipolysis in fat cells.  Endocrinology. 1991;  128 747-753
• 9 Lacasa D, Garcia E, Agli B, Giudicelli Y. Control of rat preadipocytes adipose conversion by ovarian status: regional specificity and possible involvement of the mitogen-activated protein kinase-dependent and c-fos signaling pathways.  Endocrinology. 1997;  138 2729-2734
• 10 Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, Lambert M, Lapierre P, Potier E. Medical aspects of ketone body metabolism.  Clin Invest Med. 1995;  18 193-216
• 11 Ohnuki M, Takahashi N, Yamasaki M, Fukui T. Different localization of mRNA of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-utilizing enzyme, from that of succinyl-CoA:3-oxoacid CoA-transferase in rat brain.  Biochimica et Biophysica Acta. 2005;  1729 147-153
• 12 Pasquali R. Obesity and androgens: facts and perspectives.  Fertil Steril. 2006;  85 1319-1340
• 13 Poehlman ET, Toth MJ, Gardner AW. Changes in energy balance and body composition at menopause: a controlled longitudinal study.  Ann Intern Med. 1995;  123 673-675
• 14 Rebuffe-Scrive M, Lonnroth P, Wesslau MC, Bjorntorp P. Regional adipose tissue metabolism in men and post menopausal women.  Int J Obes. 1987;  11 347-355
• 15 Rodbell M. Metabolism of isolated fat cells. Effects of hormones on glucose metabolism and lipolysis.  J Biol Chem. 1964;  239 375-380
• 16 Rosenbaum M, Nicolson M, Hirsch J, Heymsfield BB, Gallagher D, Chu F, Leibel RL. Effects of gender, body composition, and menopause on plasma concentrations of leptin.  J Clin Endocrinol Metab. 1996;  81 3424-3427
• 17 Saad MF, Damani S, Gingerich RL, Riadgabriel MG, Khan A, Boyadjian R, Jinagouda SD, Eltawil K, Rude RK, Kamdar V. Sexual dimorphism in plasma leptin concentration.  J Clin Endocrinol Metab. 1997;  82 579-584
• 18 Takahashi M, Kamei Y, Ezaki O. Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size.  Am J Physiol Endocrinol Metab. 2005;  288 E117-124
• 19 Thumelin S, Kohl C, Girard J, Pegorier JP. Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats.  J Lipid Res. 1999;  40 1071-1077
• 20 Vague J. La diffeŽrenciation sexuelle, facteur deŽterminant des formes de l’obeŽsiteŽ.  Presse Med. 1947;  53 339-340
• 21 Yamasaki M, Hasegawa S, Kitani T, Hidai K, Fukui T. Differential effects of obesity on acetoacetyl-CoA synthetase gene in rat adipose tissues.  European J Lipid Sci Tech. 2007;  109 617-622
• 22 Yamasaki M, Hasegawa S, Suzuki H, Hidai K, Saitoh Y, Fukui T. Acetoacetyl-CoA synthetase gene is abundant in rat adipose, and related with fatty acid synthesis in mature adipocytes.  Biochem Biophys Res Commun. 2005;  335 215-219

Correspondence