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An enzymatic defect in the obese (ob/ob) mouse: loss of thyroid-induced sodium- and potassium-dependent

D A York, G A Bray, Y Yukimura

    Proceedings of the National Academy of Sciences of the United States of America
    |January 1, 1978
    PubMed

    Insights

    Thyroid hormones impact key enzymes in obese mice differently. Specifically, the obese (ob/ob) mouse lacks a thyroid-dependent sodium- and potassium-dependent ATPase, explaining its metabolic abnormalities.

    Area of Science:

    • Endocrinology and Metabolism
    • Molecular Biology
    • Biochemistry

    Background:

    • Obesity is associated with altered metabolic pathways and hormonal regulation.
    • Thyroid hormones play a crucial role in regulating energy metabolism and enzyme activity.
    • Understanding enzymatic differences in obesity models is key to identifying therapeutic targets.

    Purpose of the Study:

    • To investigate the impact of thyroid status on key metabolic enzymes in different models of obesity.
    • To elucidate the role of specific enzymes, such as glycerol 3-phosphate dehydrogenase and (Na⁺ + K⁺)-ATPase, in the pathogenesis of obesity.
    • To determine if abnormalities in thyroid hormone-responsive enzymes contribute to the metabolic phenotype of genetically obese (ob/ob) mice.

    Main Methods:

    • Comparative analysis of enzyme activities in liver and kidney tissues from lean, gold thioglucose-induced obese, and genetically obese (ob/ob) mice.
    • Experimental manipulation of thyroid status: euthyroid, induced hypothyroidism, and triiodothyronine treatment.
    • Assay of glycerol 3-phosphate dehydrogenase, ouabain-suppressible sodium- and potassium-dependent ATPase, and adenylate cyclase activities.

    Main Results:

    • Glycerol 3-phosphate dehydrogenase activity was reduced in hypothyroidism and increased with triiodothyronine in all groups.
    • Lean and gold thioglucose-obese mice showed increased (Na⁺ + K⁺)-ATPase activity with triiodothyronine and decreased activity with hypothyroidism.
    • Obese (ob/ob) mice exhibited a lack of thyroid hormone-dependent increase in (Na⁺ + K⁺)-ATPase activity, which remained low.

    Conclusions:

    • The impaired response of (Na⁺ + K⁺)-ATPase to thyroid hormones in obese (ob/ob) mice is a significant finding.
    • This enzymatic deficit in obese (ob/ob) mice may underlie their characteristic metabolic abnormalities.
    • Adenylate cyclase activity was similar across groups and unaffected by thyroid hormones, suggesting a specific role for ATPase dysfunction.

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