Systemic PPARγ deletion impairs circadian rhythms of behavior and metabolism.
Compelling evidence from both human and animal studies suggests a physiological link between the circadian rhythm and metabolism but the underlying mechanism is still incompletely understood. We examined the role of PPARγ, a key regulator of energy metabolism, in the control of physiological and behavioral rhythms by analyzing two strains of whole-body PPARγ null mouse models. Systemic inactivation of PPARγ was generated constitutively by using Mox2-Cre mice (MoxCre/flox) or inducibly by using the tamoxifen system (EsrCre/flox/TM). Circadian variations in oxygen consumption, CO(2) production, food and water intake, locomotor activity, and cardiovascular parameters were all remarkably suppressed in MoxCre/flox mice. A similar phenotype was observed in EsrCre/flox/TM mice, accompanied by impaired rhythmicity of the canonical clock genes in adipose tissues and liver but not skeletal muscles or the kidney. PPARγ inactivation in isolated preadipocytes following exposure to tamoxifen led to a similar blockade of the rhythmicity of the clock gene expression. Together, these results support an essential role of PPARγ in the coordinated control of circadian clocks and metabolic pathways.
Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.
Guangrui
G
Yang
Zhanjun
Z
Jia
Toshinori
T
Aoyagi
Donald
D
McClain
Richard M
RM
Mortensen
Tianxin
T
Yang
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023061:Gene Order; D018390:Gene Targeting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics*; D010641:Phenotype; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism
D047495:PPAR gamma; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2