Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling.
Insulin and insulin-like growth factor 1 (IGF-1) have important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signalling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet-induced obesity and age- and high fat diet-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at 4 °C. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to β3-receptor stimulation. Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate.
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Jeremie
J
Boucher
Marcelo A
MA
Mori
Kevin Y
KY
Lee
Graham
G
Smyth
Chong Wee
CW
Liew
Yazmin
Y
Macotela
Michael
M
Rourk
Matthias
M
Bluher
Steven J
SJ
Russell
C Ronald
CR
Kahn
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013696:Temperature; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology*
D007328:Insulin; D007334:Insulin-Like Growth Factor I