Lack of Insulin, IGF-1 Receptors Disrupted Adipose Tissue Formation
Insulin and insulin-like growth factor 1 receptors affect adipose tissue formation.
(HealthDay News) — Mice lacking either the insulin receptor, insulin-like growth factor 1 (IGF-1) receptor, or both have disruptions in white and brown adipose tissue formation, with an almost complete absence of white adipose tissue and brown adipose tissue in mice lacking both receptors, according to a study published in Diabetes.
Jeremie Boucher, PhD, from Harvard Medical School in Boston, and colleagues used Cre-recombinase driven by the adiponectin promoter to create mice lacking insulin receptor, IGF-1 receptor, or both.
The researchers found that mice lacking IGF-1 receptor only (F-IGFRKO) had about a 25% reduction in white adipose tissue and brown adipose tissue. An almost complete absence of white adipose tissue and brown adipose tissue was seen in mice lacking both insulin receptor and IGF-1 receptor (F-IR/IGFRKO).
A 95% reduction in white adipose tissue was seen for F-IRKO mice, but they had a 50% increase in brown adipose tissue with accumulation of large unilocular lipid droplets. F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold; they also developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. In both groups, leptin treatment normalized blood glucose levels.
By 1 year of age, glucose levels also improved spontaneously, despite sustained lipodystrophy and insulin resistance.
"Loss of insulin receptor is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal brown adipose tissue function and temperature homeostasis," the researchers wrote.
One author was an employee of AstraZeneca R&D.