Brown adipose tissue-specific insulin receptor knockout in mice caused age-dependent loss of brown fat and an insulin-secretion defect resulting in progressive glucose intolerance.
This model demonstrates that insulin receptors in brown fat are crucial for adipogenesis and suggests brown adipose tissue plays a novel role in regulating insulin secretion and glucose homeostasis.
Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis.
Guerra et al. (2001) studied Glucose intolerance. Brown adipose tissue-specific insulin receptor knockout was evaluated on Phenotypic changes including brown fat loss, uncoupling protein expression, and glucose tolerance. Brown adipose tissue-specific insulin receptor knockout in mice caused age-dependent loss of brown fat and an insulin-secretion defect resulting in progressive glucose intolerance.