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Animal Models of Obesity pp 153–175Cite as

Palgrave Macmillan

Lipogenesis and hormone resistance in liver and adipose tissue of genetically obese mice

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Summary

Genetically obese rodents provide a good model of human obesity and late-onset diabetes. In the ob/ob mouse obesity can develop on fat or carbohydrate diets. On starch-based diets obesity is sustained by enhanced fatty acid synthesis in both liver and adipose tissue. The main precursors for newly synthesised fatty acid are glucose in adipose tissue and glycogen and lactate in liver, all ultimately derived from dietary glucose. Lipogenesis in the liver of normal mice is rapidly inhibited by hormones which act via cyclic-AMP (glucagon) and hormones which do not (vasopressin, angiotensin II). The liver of ob/ob mice exhibits resistance to these inhibitory effects, even after pair-feeding to maintain normal weight, whereas glycogenolysis is normally stimulated. Thus, ob/ob mice could have a selective defect among cellular membrane response mechanisms which do not involve cyclic-AMP. In contrast, lipogenesis in adipose tissue of pair-fed ob/ob mice exhibits a near-normal inhibitory response to adrenaline. Insulin-resistance in tissues of obese (ob/ob) mice, demonstrable in liver with respect to the anti-glucagon action of insulin, is likely to be a secondary consequence of obesity. The pathogenesis of obesity could involve a failure of cellular responses to extracellular agents—e.g. of those catabolic regulatory mechanisms which normally restrain insulin action in tissues.

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Author information

Authors and Affiliations

  1. Department of Biochemistry, St George’s Hospital Medical School, London, UK

    D. A. Hems

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  1. D. A. Hems
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Editors and Affiliations

  1. Medical Research Council Laboratory Animals Centre, Carshalton, Surrey, UK

    Michael F. W. Festing B.Sc., M.Sc., Ph.D., M.I.S., M.I.Biol.

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© 1979 The Medical Research Council

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Hems, D.A. (1979). Lipogenesis and hormone resistance in liver and adipose tissue of genetically obese mice. In: Festing, M.F.W. (eds) Animal Models of Obesity. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-04201-2_10

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