Abstract
Triiodothyronine (T3) is known to increase liver lipogenic enzyme gene expression both in vivo and in tissue culture. Conflicting results have been reported on the effect of T3 on lipogenic enzyme gene expression in white adipose tissue. The results presented
in this paper indicate that administration of pharmacological doses of T3 in rats leads to increased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC),
ATP-citrate lyase (ACL) and malic enzyme (ME) activity in white adipose tissue. The
increase in lipogenic enzyme activity was associated with increased FAS, ACC, ACL
and ME mRNA levels. The response was dose-dependent. Activity of lipogenic enzyme
and the lipogenic enzyme mRNA levels were positively correlated to serum T3 concentration. The in vivo effect of T3 on lipogenic enzyme gene expression could be reproduced in primary white rat adipocyte
culture. In conclusion, the results presented in this paper indicate that T3 exerts a stimulatory effect on lipogenic enzyme gene expression in white adipose
tissue both in vivo and in tissue culture. Significant effects of T3 on lipogenic enzyme gene expression were only observed in the presence of relatively
high (pharmacological) concentrations of the hormone.
Key words
Triiodothyronine - lipogenic enzyme activity - mRNA - white adipose tissue - rat adipocytes
References
- 1
Mariash C N, Kaiser F E, Oppenheimer J H.
Comparison of the response characteristics of four lipogenic enzymes to 3,5,3’-triiodothyronine
administration: evidence for variable degrees of amplification of the nuclear 3,5,3’-triiodothyronine
signal.
Endocrinology.
1980;
106
22-27
- 2
Diamant S, Gorin E, Shafrir E.
Enzyme activities related to fatty-acid synthesis in liver and adipose tissue of rats
treated with triiodothyronine.
Eur J Biochem.
1972;
26
553-559
- 3
Wilson S B, Back D W, Morris S M Jr, Swierczynski J, Goodridge A G.
Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Expression
of the fatty acid synthase gene is regulated at both translational and pretranslational
steps.
J Biol Chem.
1986;
261
15179-15182
- 4
Stapleton S R, Mitchell D A, Salati L M, Goodridge A G.
Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick
embryo hepatocytes in culture. Insulin and insulin-like growth factor amplify that
effect.
J Biol Chem.
1990;
265
18442-18446
- 5
Swierczynski J, Mitchell D A, Reinhold D S, Salati L M, Stapleton S R, Klautky S A,
Struve A E, Goodridge A G.
Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme
A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription
is the affected step.
J Biol Chem.
1991;
266
17459-17466
- 6
Hillgartner F B, Chen W, Goodridge A G.
Overexpression of the alpha-thyroid hormone receptor in avian cell lines. Effects
on expression of the malic gene are selective and cell-specific.
J Biol Chem.
1992;
267
12299-12306
- 7
Freake H C, Moon Y K.
Hormonal and nutritional regulation of lipogenic enzyme mRNA levels in rat primary
white and brown adipocytes.
J Nutr Sci Vitaminol (Tokyo).
2003;
49
40-46
- 8
Jiang W, Miyamoto T, Kakizawa T, Sakuma T, Nishio S-I, Takeda T.
Expression of thyroid hormone receptor α in 3T3-L1 adipocytes; triiodothyronine increases the expression of lipogenic enzyme and
triglyceride accumulation.
J Endocrinol.
2004;
182
295-302
- 9
Moustaid N, Sul H S.
Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine.
J Biol Chem.
1991;
266
18550-18554
- 10
Gharbi-Chihi J, Facchinetti T, Berge-Lefranc J L, Bonne J, Torresani J.
Triiodothyronine control of ATP-citrate lyase and malic enzyme during differentiation
of a murine preadipocyte cell line.
Horm Metab Res.
1991;
23
423-427
- 11
Gharbi-Chihi J, Chabaud O, Torresani J.
The role of triiodothyronine in the regulation of synthesis rate and translatable
mRNA level of fatty acid synthase in a preadipocyte cell line.
Biochim Biophys Acta.
1984;
783
26-35
- 12
Flores-Delgado G, Marsch-Moreno M, Kuri-Harcuch W.
Thyroid hormone stimulates adipocyte differentiation of 3T3 cells.
Mol Cell Biochem.
1987;
76
35-43
- 13
Roncari D AK, Murthy V K.
Effects of thyroid hormone on enzymes involved in fatty acid and glycerolipid synthesis.
J Biol Chem.
1975;
250
4134-4138
- 14
Llobera M, Muniesa A, Herrera E.
Effects of hyperthyroidism on in vivo lipogenesis in fed and fasted rats.
Horm Metab Res.
1979;
11
628-634
- 15
Mooradian A D, Albert S G.
The age-related changes in lipogenic enzymes: the role of dietary factors and thyroid
hormone responsivness.
Mech Ageing Dev.
1999;
108
139-149
- 16
Freake H C, Schwartz H L, Oppenheimer J H.
The regulation of lipogenesis by thyroid hormone and its contribution to thermogenesis.
Endocrinology.
1989;
125
2868-2874
- 17
Gnoni G V, Landriscina C, Quagliariello E.
Fatty acid biosynthesis in adipose tissue and lung subcellular fractions of thyrotoxic
rats.
FEBS Lett.
1980;
122
37-40
- 18
Blennemann B, Moon Y K, Freake H C.
Tissue specific regulation of fatty acid synthesis by thyroid hormone.
Endocrinology.
1992;
130
637-643
- 19
Blennemann B, Leahy P, Kim T-S, Freake H C.
Tissue specific regulation mRNAs by thyroid hormone.
Mol Cell Endocrinol.
1995;
110
1-8
- 20
Dugail I, Quignard-Boulange A, Le Liepvre X, Ardouin B, Lavau M.
Gene expression of lipid storage-related enzymes in adipose tissue of the genetically
obese Zucker rat co-ordinated increase in transcriptional activity and potentiation
by hyperinsulinemia.
Biochem J.
1992;
281
607-611
- 21
Kochan Z, Karbowska J, Swierczynski J.
Unusual increase of lipogenesis in rat white adipose tissue after multiple cycles
of starvation-refeeding.
Metabolism.
1997;
46
10-17
- 22
Rodbell M.
Localisation of lipoprotein lipase in fat cells of rat adipose tissue.
J Biol Chem.
1964;
239
753-755
- 23
Karbowska J, Kochan Z, Zelewski L, Swierczynski J.
Tissue specific effect of clofibrate on rat lipogenic enzyme gene expression.
Eur J Pharmacol.
1999;
370
329-336
- 24
Karbowska J, Kochan Z, Swierczynski J.
Differential effect of clofibrate on acetyl-CoA carboxylase mRNA level in rat white
and brown adipose tissue.
Life Sci.
2000;
66
545-552
- 25
Trayhurn P, Duncan J S, Rayner D V.
Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue
of mice: mediation by the sympathetic system.
Biochem J.
1995;
311
729-733
- 26
Chomczynski P, Sacchi N.
Single-step method of RNA isolation by guanidinium thiocyanate-phenol-chloroform extraction.
Anal Biochem.
1987;
162
156-159
- 27
Kochan Z, Karbowska J, Swierczynski J.
Effect of clofibrate on malic enzyme and leptin mRNA levels in rat brown and white
adipose tissue.
Horm Metab Res.
1999;
31
538-542
- 28
Zelewski L, Swierczynski J.
The effect of clofibrate feeding on the NADP-linked dehydrogenases activity in rat
tissue.
Biochim Biophys Acta.
1983;
758
152-157
- 29
Korczynska J, Stelmanska E, Swierczynski J.
Differential effect of long-term food restriction on fatty acid synthase and leptin
gene expression in rat white adipose tissue.
Horm Metab Res.
2003;
35
593-597
- 30
Petty K J, Desvergne B, Mistuhashi T, Nikodem V M.
Identification of a thyroid hormone response element in the malic enzyme gene.
J Biol Chem.
1990;
265
7395-7400
- 31
Xiong S, Chirala S S, Hsu M H, Wakil S J.
Identification of thyroid hormone response elements in the human fatty acid synthase
promoter.
Proc Nat Acad Sci USA.
1998;
95
12260-12265
- 32
Zhang Y, Yin L, Hillgartner F B.
Thyroid hormone stimulates acetyl-CoA carboxylase-α transcription in hepatocytes by
modulating the composition of nuclear receptor complex bound to a thyroid hormonr
response element.
J Biol Chem.
2001;
276
974-983
Julian Swierczynski
Department of Biochemistry · Medical University of Gdansk
Debinki 1 · 80-211 Gdansk · Poland
Phone: +48 (58) 349 14 62
Fax: +48 (58) 349 14 65
Email: juls@amg.gda.pl