Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes

Junichi Matsuda, Kiminori Hosoda, Hiroshi Itoh, Cheol Son, Kentaro Doi, Ikuko Hanaoka, Gen Inoue, Haruo Nishimura, Yasunao Yoshimasa, Yukio Yamori, Hiroyuki Odaka, Kazuwa Nakao

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg kg-1 day-1 pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 ± 8, 45 ± 13, and 76 ± 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10-5 to 10-4 mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.

Original languageEnglish
Pages (from-to)1809-1814
Number of pages6
JournalDiabetes
Volume47
Issue number11
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Thiazolidinediones
pioglitazone
White Adipose Tissue
Adipocytes
Wistar Rats
Brown Adipose Tissue
Messenger RNA
Genes
Energy Metabolism
Intra-Abdominal Fat
Gene Expression
Leptin Receptors
Glucose
Skeletal Muscle
Type 2 Diabetes Mellitus
Uncoupling Protein 3
Subcutaneous Fat
Mitochondrial Proteins
Mitochondrial Membranes
Electron Transport

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes. / Matsuda, Junichi; Hosoda, Kiminori; Itoh, Hiroshi; Son, Cheol; Doi, Kentaro; Hanaoka, Ikuko; Inoue, Gen; Nishimura, Haruo; Yoshimasa, Yasunao; Yamori, Yukio; Odaka, Hiroyuki; Nakao, Kazuwa.

In: Diabetes, Vol. 47, No. 11, 1998, p. 1809-1814.

Research output: Contribution to journalArticle

Matsuda, J, Hosoda, K, Itoh, H, Son, C, Doi, K, Hanaoka, I, Inoue, G, Nishimura, H, Yoshimasa, Y, Yamori, Y, Odaka, H & Nakao, K 1998, 'Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes', Diabetes, vol. 47, no. 11, pp. 1809-1814. https://doi.org/10.2337/diabetes.47.11.1809
Matsuda, Junichi ; Hosoda, Kiminori ; Itoh, Hiroshi ; Son, Cheol ; Doi, Kentaro ; Hanaoka, Ikuko ; Inoue, Gen ; Nishimura, Haruo ; Yoshimasa, Yasunao ; Yamori, Yukio ; Odaka, Hiroyuki ; Nakao, Kazuwa. / Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes. In: Diabetes. 1998 ; Vol. 47, No. 11. pp. 1809-1814.
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abstract = "Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg kg-1 day-1 pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 ± 8, 45 ± 13, and 76 ± 6{\%}) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10-5 to 10-4 mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.",
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T1 - Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes

AU - Matsuda, Junichi

AU - Hosoda, Kiminori

AU - Itoh, Hiroshi

AU - Son, Cheol

AU - Doi, Kentaro

AU - Hanaoka, Ikuko

AU - Inoue, Gen

AU - Nishimura, Haruo

AU - Yoshimasa, Yasunao

AU - Yamori, Yukio

AU - Odaka, Hiroyuki

AU - Nakao, Kazuwa

PY - 1998

Y1 - 1998

N2 - Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. Uncoupling of electron transport and ATP synthesis has been reported to increase glucose uptake, suggesting that UCP may be involved in glucose metabolism. Thiazolidinediones (TZDs), which are insulin-sensitizing agents for NIDDM, have been reported to increase energy expenditure. To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg kg-1 day-1 pioglitazone, a TZD derivative. Basal UCP3 mRNA levels were significantly lower (38 ± 8, 45 ± 13, and 76 ± 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. In pioglitazone-treated Wistar fatty rats, UCP3 mRNA levels were significantly increased by 2.1-, 2.0-, and 1.6-fold in the epididymal WAT, retroperitoneal WAT, and BAT, respectively, as compared with those in nontreated fatty rats. In pioglitazone-treated lean rats, UCP3 mRNA levels were significantly increased by 1.3-fold in the BAT as compared with those in nontreated lean rats. No significant change of UCP2 mRNA levels was observed in pioglitazone-treated fatty and lean rats. In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10-5 to 10-4 mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. The present study suggests the involvement of UCP3 in the effects of TZDs on energy and glucose metabolism.

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