Dose-related steady states of fat loss in long-term leptin-treated <Emphasis Type="Italic">ob/ob</Emphasis> mice: Leptin resistance or desensitization versus counterregulatory signaling |
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Authors: | Sandra?Eiden Email author" target="_blank">Eckhart?SimonEmail author Ingrid?Schmidt |
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Institution: | (1) Max-Planck-Institut fuer Herz- und Lungenforschung, W.G. Kerckhoff-Institut, Parkstr.1, 61231 Bad Nauheim, Germany |
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Abstract: | We tried to unravel why leptin’s fat store depleting action levels off in the course of long-term applications. Supplying
leptin by minipump infusion for 2 months to ob/ob mice at rates between 115 pmol day−1 and 460 pmol day−1 resulted in stable plasma leptin levels between 0.2 ng ml−1 and 8 ng ml−1. Initial treatment effects were leptin dose-dependent reductions in food intake and body mass, especially in fat content,
followed by re-increases of food intake to levels only 4–18% below pre-treatment levels. Decreased body mass subsequently
stabilized dose-dependently with body fat contents between 4% and 33% showing that total fat depletion was not a precondition
for the progressive reduction of leptin-induced anorexia. Oxygen consumption measurements excluded contributions of enhanced
energy dissipation to fat depletion. Plasma insulin concentrations declined from excessively high pre-treatment levels to
steady, leptin dose-dependent levels within the normal range. Temporary anorexia in response to repeated additional 1-day
leptin injections (100 pmol g−1 day−1) remained unchanged throughout long-term leptin infusion. Among various alternatives considered to explain the adipostatic
equilibrium attained at new, dose-dependent levels under long-term leptin treatment, interaction between the leptin signal
and at least one counteracting signal increasing with fat depletion is proposed as the most plausible working hypothesis. |
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Keywords: | Anorexigenic Orexigenic Energy expenditure Energy balance |
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