Up‐regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator‐activated receptor ligands and 9‐<i>cis</i> retinoic acid in L6 myotubes

Nagase, Itsuro; Yoshida, Shigeru; Cañas, Xavier; Irie, Yukiko; Kimura, Kazuhiro; Yoshida, Toshihide; Saito, Masayuki

doi:10.1016/s0014-5793(99)01477-5

Cited by 74 publications

(72 citation statements)

References 29 publications

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“…Moreover, Weigle et al [23] demonstrated that elevation of circulating free fatty acid levels induced by Intralipid plus heparin infusion mimicked the increased expression of muscle UCP3 seen after fasting. Being consistent with these in vivo results, we reported that oleic acid and a non-metabolizable α-bromopalmitic acid induced UCP3 mRNA in cultured L6 myocytes [16]. Induction of UCP2 mRNA in L6 cells was also reported by Camirand et al [4].…”

Section: Discussionsupporting

confidence: 91%

“…Because the β3-AR is generally recognized to be expressed in adipocytes but not in myocytes, the effect of CL in vivo is not due to a direct action of this drug on myocytes thorough the β3-AR. In fact, the UCP2 and UCP3 mRNA levels in cultured L6 myocytes were not influenced by the treatment of the cells with CL in vitro [16]. It is therefore more likely that CL stimulates UCP expression of muscle in vivo through some indirect action.…”

Section: Discussionmentioning

confidence: 93%

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.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

Nakamura

Nagase

Asano

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Chronic stimulation of the β3-adrenergic receptor (AR) in obese animals resulted in a reduced adiposity associated with an increased expression of thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, the mRNA expression of newly cloned UCP isoforms (UCP2 and UCP3) were examined in obese yellow KK and C57BL control mice. UCP2 mRNA was found in all tissues examined, with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3 mRNA was expressed in skeletal muscle, heart and brown adipose tissue similarly in the two mouse strains. Daily injection of a selective β3-adrenergic agonist, CL316,243 (0.1 mg/kg), for 10 days resulted in a marked reduction of white fat pad weight and 1.8~4.8-fold increase in the mRNA levels of UCP2 and UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3 mRNA levels was found in brown and white adipose tissues. It was also found that CL316,243 injection produced a marked and sustained elevation of the plasma free fatty acid level. These results, together with our previous findings of the fatty acid-induced UCP expression in a myocyte cell line in vitro, suggest that the β3-AR agonist-induced UCP expression in skeletal muscle may be mediated through the elevated plasma free fatty acids. It was also suggested that anti-obesity effect of β3-AR agonists is attributable to increased thermogenesis not only by UCP1 but also by UCP2 and UCP3.KEY WORDS: adipose tissue, β3-adrenergic agonist, fatty acid, obese mouse, uncoupling protein.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 93%

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

Nakamura

Nagase

Asano

et al. 2001

The Journal of Veterinary Medical Science

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“…These results are in agreement with studies in vitro showing induction of UCP3 expression by RA in differentiated myotubes in cell culture. 24,25 Notwithstanding the possibility of post-transcriptional effects, the effect of retinoids on UCP3 expression may reflect enhanced activity of the retinoic acid receptor: retinoid X receptor (RAR:RXR) heterodimers and=or of peroxisome proliferator-activated receptor: RXR (PPAR:RXR) heterodimers, for both of which response elements have been described in the UCP3 gene promoter, 25,39 as well as in the UCP1 gene promoter (see ref. 1).…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of muscle uncoupling protein 3 gene expression in mice following high fat diet, dietary vitamin A supplementation and acute retinoic acid-treatment

et al. 2003

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OBJECTIVE:To analyse the impact of vitamin A supplementation of both a normal fat (NF) diet and a high fat (HF) diet and of acute retinoic acid (RA)-treatment on the expression of uncoupling protein 3 (UCP3) in mice. DESIGN: C57BL=6J mice were fed for 18 weeks a NF or a HF diet (10 and 45 energy% as fat, respectively), both with the normal vitamin A content or an excess vitamin A (8 mg and 320 mg retinyl palmitate=kg diet, respectively). Body weight and energy intake were recorded periodically. UCP3 mRNA and UCP3 protein levels in skeletal muscle (soleus=gastrocnemius) were analysed, as well as UCP1, UCP2 and UCP3 mRNA levels in interscapular brown adipose tissue (BAT), and UCP2 mRNA, UCP2 protein and leptin mRNA levels in white adipose tissue (WAT) depots. The effect of acute RA-treatment (100 mg=kg=day, 4 days) on UCP3 mRNA levels in skeletal muscle and BAT of NMRI mice was also assessed. RESULTS: Vitamin A supplementation of a NF diet led to increased levels of UCP3 mRNA and UCP3 protein in muscle, UCP1 mRNA in BAT, and UCP2 mRNA in inguinal WAT, but had no impact on body weight or adiposity of B6 mice. HF diet promoted obesity and increased levels of UCP3 mRNA and UCP3 protein in skeletal muscle, and of the mRNAs for all three UCPs in BAT. Supplementing the HF diet with vitamin A had little effect on the final obesity reached and did not lead to further increases of muscle UCP3 mRNA nor BAT UCP1 mRNA over the levels achieved with the non-supplemented HF diet. Adipose leptin mRNA levels were down regulated after vitamin A supplementation, independently of the fat content of the diet. Up-regulation of muscle, but not BAT, UCP3 mRNA levels was also found after acute RA-treatment in NMRI mice. CONCLUSION:The results provide evidence of a stimulatory effect of retinoids on muscle UCP3 expression in vivo, and a differential retinoid-regulation of the UCP3 gene in muscle and BAT.

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“…10,15,16,23,24 The mechanism by which PPAR ligands up-regulate UCP gene expression is complex. PPAR is a member of the nuclear receptor superfamily that includes receptors for the steroid, thyroid and retinoid hormones.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, UCP3 in L 6 myotubes has been shown to be up-regulated by thyroid hormone, ligands of peroxisome proliferator-activated receptor (PPAR) and retinoic acid. 15 Despite the increasing number of reports on UCP2 and UCP3, the molecular and=or cellular mechan-isms regulating UCP2 gene expression in skeletal muscle are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

Hatakeyama

Scarpace

2001

Int J Obes

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OBJECTIVE:To increase the understanding of the transcriptional regulation of UCP2 gene expression in skeletal muscle cells, we examined the effect of all-trans-retinoic acid (tRA), a ligand (after the conversion to 9-cis-RA) of the retinoid X receptor (RXR), and linolenic acid, a polyunsaturated fatty acid and peroxisome proliferator-activated receptors (PPARs) ligand, on the expression of UCP2 mRNA in cultured L 6 myotubes. RESEARCH METHODS AND PROCEDURES: UCP2 gene expression in L 6 myotubes was confirmed by Northern blot analysis. The time-and concentration-dependency of tRA and linolenic acid on UCP2 gene expression was assessed by dot blot quantification. The mRNA levels of PPAR subtypes (a, g and d) were determined by RT-PCR. RESULTS: tRA induced UCP2 gene expression in a time-and concentration-dependent manner. Similar to tRA, UCP2 mRNA was markedly increased by 0.5 mM linolenic acid. In L 6 myotubes, PPARd mRNA was abundant, whereas PPARa mRNA was lower and PPARg mRNA was minimal. CONCLUSIONS: UCP2 mRNA expression in L 6 myotubes is up-regulated by tRA and linolenic acid, possibly through a mechanism involving PPAR and RXRs.

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Up‐regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator‐activated receptor ligands and 9‐cis retinoic acid in L6 myotubes

Cited by 74 publications

References 29 publications

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

Up-regulation of muscle uncoupling protein 3 gene expression in mice following high fat diet, dietary vitamin A supplementation and acute retinoic acid-treatment

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

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