Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-02, Vol.102 (7), p.2496-2501
• Main Authors: Macdonald, L.E, Wortley, K.E, Gowen, L.C, Anderson, K.D, Murray, J.D, Poueymirou, W.T, Simmons, M.V, Barber, D, Valenzuela, D.M, Economides, A.N
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; blood glucose; blood lipids; Blood pressure; Body composition; body fat; Body Weight; Bones; Diet; Dietary Fats - administration & dosage; Gene Expression; gene overexpression; Genes, Reporter; Glycoproteins; Glycoproteins - genetics; Heart rate; high fat diet; Hormone metabolism; Hormones; Insulin; Lac Operon; Male animals; Medical research; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Biological; Molecular Sequence Data; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; orphan glycoprotein hormone; Peptide Hormones - genetics; Phenotype; Rodents; Thyroid; thyroid gland; Thyroid hormones; transgenic animals; weight gain
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0409849102

We identified a glycoprotein hormone beta-subunit (OGH, also called GPB5) that, as a heterodimer with the alpha-subunit GPA2, serves as a second ligand for the thyroid-stimulating hormone receptor. Mice in which the OGH gene is deleted (OGH(-/-)) are indistinguishable from WT littermates in body weight, response to high-fat diet, metabolic parameters, body composition, and insulin tolerance. Mice engineered to transgenically globally overexpress OGH (OGH-TG) develop approximately equal to 2-fold elevations in their basal thyroid levels and weigh slightly less than WT littermates despite increased food intake because of an increase in their metabolic rates. Moreover, when OGH-TG mice are challenged with a high-fat diet, they gain significantly less weight and body fat than their WT littermates. The OGH-TG mice also have reduced blood glucose, insulin, cholesterol, and triglycerides. In contrast to other approaches in which the thyroid axis is activated, OGH-TG mice exhibit only minor changes in heart rate and blood pressure. Our findings suggest that constitutive low-level activation of the thyroid axis (via OGH or other means) may provide a beneficial therapeutic approach for combating diet-induced obesity.