Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice

G. Kim, Y. H. Lee, M. R. Yun, J. Y. Lee, E. G. Shin, B. W. Lee, E. S. Kang, B. S. Cha

Research output: Contribution to journalArticle

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Abstract

Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg '1 daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18 F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18 F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalInternational Journal of Obesity
Volume42
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

Fingerprint

Brown Adipose Tissue
Adipose Tissue
White Adipose Tissue
Brown Adipocytes
Insulin Resistance
Subcutaneous Fat
lobeglitazone
2,4-thiazolidinedione
Beige Adipose Tissue
White Adipocytes
Macrophages
Glycemic Index
Weights and Measures
Thermogenesis
PPAR gamma
Deoxyglucose
Insulin-Secreting Cells
Adipocytes
Positron-Emission Tomography
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Kim, G. ; Lee, Y. H. ; Yun, M. R. ; Lee, J. Y. ; Shin, E. G. ; Lee, B. W. ; Kang, E. S. ; Cha, B. S. / Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice. In: International Journal of Obesity. 2018 ; Vol. 42, No. 3. pp. 542-551.
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title = "Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice",
abstract = "Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg '1 daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18 F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18 F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.",
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Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice. / Kim, G.; Lee, Y. H.; Yun, M. R.; Lee, J. Y.; Shin, E. G.; Lee, B. W.; Kang, E. S.; Cha, B. S.

In: International Journal of Obesity, Vol. 42, No. 3, 01.03.2018, p. 542-551.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice

AU - Kim, G.

AU - Lee, Y. H.

AU - Yun, M. R.

AU - Lee, J. Y.

AU - Shin, E. G.

AU - Lee, B. W.

AU - Kang, E. S.

AU - Cha, B. S.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg '1 daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18 F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18 F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

AB - Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg '1 daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18 F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18 F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

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