Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a crucial role in adipocyte differentiation, glucose metabolism, and other physiological processes. To further explore the role of PPARgamma in adipose tissues, we used a Cre/loxP strategy to generate adipose-specific PPARgamma knockout mice. These animals exhibited marked abnormalities in the formation and function of both brown and white adipose tissues. When fed a high-fat diet, adipose-specific PPARgamma knockout mice displayed diminished weight gain despite hyperphagia, had diminished serum concentrations of both leptin and adiponectin, and did not develop glucose intolerance or insulin resistance. Characterization of in vivo glucose dynamics pointed to improved hepatic glucose metabolism as the basis for preventing high-fat diet-induced insulin resistance. Our findings further illustrate the essential role for PPARgamma in the development of adipose tissues and suggest that a compensatory induction of hepatic PPARgamma may stimulate an increase in glucose disposal by the liver.
Jones
Julie R
JR
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Barrick
Cordelia
C
Kim
Kyoung-Ah
KA
Lindner
Jill
J
Blondeau
Bertrand
B
Fujimoto
Yuka
Y
Shiota
Masakazu
M
Kesterson
Robert A
RA
Kahn
Barbara B
BB
Magnuson
Mark A
MA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003433:Crosses, Genetic; D004041:Dietary Fats; D002149:Energy Intake; D004734:Energy Metabolism; D017353:Gene Deletion; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006946:Hyperinsulinism / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D047495:PPAR gamma / Q000172:deficiency* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D047495:PPAR gamma; D014280:Triglycerides