Chronic leptin treatment does not prevent the development of obesity in transgenic mice with brown fat deficiency |
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Authors: | A Hamann B Büsing C Kausch J Ertl G Preibisch H Greten S Matthaei |
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Institution: | (1) Department of Medicine, University of Hamburg, Hamburg, Germany, DE;(2) Hoechst AG, TA Metabolic Diseases, Frankfurt/Main, Germany, DE |
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Abstract: | Summary With the exception of ob/ob mice, circulating plasma leptin is elevated in all other obese rodents as well as in obese humans, suggesting that leptin
resistance rather than leptin deficiency is a characteristic feature of obesity. The exact molecular mechanisms leading to
leptin resistance and the applicability of exogenous leptin to overcome resistance to the anorectic effect of the hormone,
are insufficiently characterized. The aim of this study was to investigate whether chronic leptin administration could prevent
the development of obesity and its associated disorders in transgenic mice with toxigene mediated ablation of brown adipose
tissue (BAT). Daily injections of leptin were started at the age of 6 weeks, when body weight, food intake and plasma leptin
levels of transgenics were not different from control mice. Over the next 6 weeks, leptin treated transgenics showed the same
excessive body weight gain as transgenic mice injected with saline. Leptin treatment was furthermore not able to prevent the
development of hyperphagia, hyperglycaemia, hyperinsulinaemia and hyperlipidaemia in transgenic mice. In contrast, control
mice injected with leptin had significantly lower body weight, food intake and plasma triglycerides than those treated with
saline. In summary, leptin treatment was not able to prevent the development of obesity and its associated abnormalities in
transgenic mice with BAT deficiency. This data suggests that intact BAT function is of critical importance for leptin's effect
on food intake and energy expenditure, and that primary dysfunction of BAT is associated with leptin resistance, even when
hyperleptinaemia is not yet present. Diabetologia (1997) 40: 810–815]
Received: 11 November 1996 and in final revised form: 8 April 1997 |
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Keywords: | Leptin obesity brown fat transgenic mice insulin resistance hyperphagia leptin resistance |
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