Targeted inhibition of galectin 1 by thiodigalactoside dramatically reduces body weight gain in diet-induced obese rats

R. Mukherjee, S. W. Kim, T. Park, M. S. Choi, J. W. Yun

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background:Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats.Methods:Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats.Results:Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg -1) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3% reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure.Conclusion:GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.

Original languageEnglish
Pages (from-to)1349-1358
Number of pages10
JournalInternational Journal of Obesity
Volume39
Issue number9
DOIs
Publication statusPublished - 2015 Sep 10

Fingerprint

Galectin 1
Weight Gain
Body Weight
Diet
High Fat Diet
Adipocytes
Obesity
Adipogenesis
thiodigalactoside
Lipogenesis
Peptide Mapping
Thermogenesis
Intraperitoneal Injections
Immunoprecipitation
Lectins
Energy Metabolism
Sprague Dawley Rats
Adipose Tissue
Real-Time Polymerase Chain Reaction
Neoplasms

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "Targeted inhibition of galectin 1 by thiodigalactoside dramatically reduces body weight gain in diet-induced obese rats",
abstract = "Background:Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats.Methods:Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats.Results:Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg -1) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3{\%} reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure.Conclusion:GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.",
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Targeted inhibition of galectin 1 by thiodigalactoside dramatically reduces body weight gain in diet-induced obese rats. / Mukherjee, R.; Kim, S. W.; Park, T.; Choi, M. S.; Yun, J. W.

In: International Journal of Obesity, Vol. 39, No. 9, 10.09.2015, p. 1349-1358.

Research output: Contribution to journalArticle

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AU - Kim, S. W.

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AU - Choi, M. S.

AU - Yun, J. W.

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N2 - Background:Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats.Methods:Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats.Results:Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg -1) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3% reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure.Conclusion:GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.

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