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Animal Models

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

International Journal of Obesity volume 39, pages 1349–1358 (2015)Cite this article

Subjects

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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Acknowledgements

This work was supported by the Mid-career Researcher Program (2013R1A2A2A05004195) and by the SRC Program (Center for Food & Nutritional Genomics, grant number 2015R1A5A6001906) through an NRF grant funded by the Ministry of Science, ICT and Future Planning, Korea.

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Authors and Affiliations

  1. Department of Biotechnology, Daegu University, Kyungsan, Republic of Korea

    R Mukherjee, S W Kim & J W Yun

  2. Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea

    T Park

  3. Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu, Republic of Korea

    M S Choi

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Correspondence to J W Yun.

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Mukherjee, R., Kim, S., Park, T. et al. Targeted inhibition of galectin 1 by thiodigalactoside dramatically reduces body weight gain in diet-induced obese rats. Int J Obes 39, 1349–1358 (2015). https://doi.org/10.1038/ijo.2015.74

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