Overfeeding rapidly induces leptin and insulin resistance

J Wang, S Obici, K Morgan, N Barzilai, Z Feng… - Diabetes, 2001 - Am Diabetes Assoc
J Wang, S Obici, K Morgan, N Barzilai, Z Feng, L Rossetti
Diabetes, 2001Am Diabetes Assoc
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 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.
Am Diabetes Assoc