Brown fat is a thermogenic tissue that generates heat to maintain body 
temperature in cold environments and dissipate excess energy in response to 
overfeeding. We have addressed the role of the IGFIR in the brown fat 
development and function. Mice lacking IGFIR exhibited normal brown adipose 
tissue/body weight in knockout (KO) vs control mice. However, lack of IGFIR 
decreased uncoupling protein 1 expression in interscapular brown fat and beige 
cells in inguinal fat. More importantly, the lack of IGFIR resulted in an 
impaired cold acclimation. No differences in the total fat volume were found in 
the KO vs control mice. Epididymal fat showed larger adipocytes but with a lower 
number of adipocytes in KO vs control mice at age 12 months. In addition, KO 
mice showed a sustained moderate hyperinsulinemia and hypertriglyceridemia upon 
time and hepatic insulin insensitivity associated with lipid accumulation, with 
the outcome of a global insulin resistance. In addition, we found that the 
expression of uncoupling protein 3 in the skeletal muscle was decreased and its 
expression was increased in the heart in parallel with the expression of beta-2 
adrenergic receptors. Upon nonobesogenic high-fat diet, we found a severe 
insulin resistance in the liver and in the skeletal muscle, but unchanged 
insulin sensitivity in the heart. In conclusion, our data suggest that IGFIR it 
is not an essential growth factor in the brown fat development in the presence 
of the IR and very high plasma levels of IGF-I, but it is indispensable for full 
brown fat functionality.