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In vivo modulation of Hmgic reduces obesity

Nature Genetics volume 24, pages 377–380 (2000)Cite this article

Abstract

The HMGI family of proteins consists of three members1,2, HMGIC, HMGI and HMGI(Y), that function as architectural factors3,4,5 and are essential components of the enhancesome6,7. HMGIC is predominantly expressed in proliferating, undifferentiated mesenchymal cells and is not detected in adult tissues8,9. It is disrupted and misexpressed in a number of mesenchymal tumour cell types10,11,12, including fat-cell tumours12 (lipomas). In addition Hmgic–/– mice have a deficiency in fat tissue13. To study its role in adipogenesis and obesity, we examined Hmgic expression in the adipose tissue of adult, obese mice. Mice with a partial or complete deficiency of Hmgic resisted diet-induced obesity. Disruption of Hmgic caused a reduction in the obesity induced by leptin deficiency (Lepob/Lepob) in a gene-dose–dependent manner. Our studies implicate a role for HMGIC in fat-cell proliferation, indicating that it may be an adipose-specific target for the treatment of obesity.

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Figure 1: Hmgic expression in the white adipose tissue (WAT) of obese mice.
Figure 2: Hmgic−/− and Hmgic+/− mice are resistant to diet-induced obesity.
Figure 3
Figure 4: Growth curves of Hmgic+/−, Lepob/+ intercross progeny.
Figure 5: Adiposity of Hmgic−/−, Lepob/Lepob and Hmgic+/−, Lepob/Lepob mice is reduced compared with that of Lepob/Lepob mice.
Figure 6: A model for HMGIC in adipogenesis and obesity.

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Acknowledgements

We thank J. D'Armiento, HMGene, Inc. and members of the laboratory for a critical reading of the manuscript. K.C. is supported by National Institutes of Health grant CA77929 and NJ Commission on Science and Technology.

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  1. Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA

    Ashim Anand & Kiran Chada

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Correspondence to Kiran Chada.

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Anand, A., Chada, K. In vivo modulation of Hmgic reduces obesity. Nat Genet 24, 377–380 (2000). https://doi.org/10.1038/74207

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