TY - JOUR
T1 - Overfeeding rapidly induces leptin and insulin resistance
AU - Wang, Jiali
AU - Obici, Silvana
AU - Morgan, Kimyata
AU - Barzilai, Nir
AU - Feng, Zhaohui
AU - Rossetti, Luciano
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001/12
Y1 - 2001/12
N2 - In common forms of obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia coexist. Here, we demonstrate rapid induction of insulin and leptin resistance by short-term overfeeding. After 3 and 7 days on the assigned diet regimen, rats were tested for their biological responses to acute elevations in plasma insulin and leptin concentrations. Severe resistance to the metabolic effects of both leptin and insulin ensued after just 3 days of overfeeding. During the insulin clamp studies, glucose production was decreased by ∼70% in control rats and 28-53% in overfed rats. Similarly, leptin infusion doubled the contribution of gluconeogenesis to glucose output in control rats but failed to modify gluconeogenesis in overfed animals. These findings demonstrate a paradoxical and rapid collapse of the leptin system in response to nutrient excess. This partial failure is tightly coupled with the onset of insulin resistance.
AB - In common forms of obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia coexist. Here, we demonstrate rapid induction of insulin and leptin resistance by short-term overfeeding. After 3 and 7 days on the assigned diet regimen, rats were tested for their biological responses to acute elevations in plasma insulin and leptin concentrations. Severe resistance to the metabolic effects of both leptin and insulin ensued after just 3 days of overfeeding. During the insulin clamp studies, glucose production was decreased by ∼70% in control rats and 28-53% in overfed rats. Similarly, leptin infusion doubled the contribution of gluconeogenesis to glucose output in control rats but failed to modify gluconeogenesis in overfed animals. These findings demonstrate a paradoxical and rapid collapse of the leptin system in response to nutrient excess. This partial failure is tightly coupled with the onset of insulin resistance.
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U2 - 10.2337/diabetes.50.12.2786
DO - 10.2337/diabetes.50.12.2786
M3 - Article
C2 - 11723062
AN - SCOPUS:0035654626
VL - 50
SP - 2786
EP - 2791
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 12
ER -