Systemic PPARγ deletion causes severe disturbance in fluid homeostasis in mice.
The pharmacological action of peroxisome proliferator-activated receptor (PPAR)γ in promoting sodium and water retention is well documented as highlighted by the major side-effect of body weight gain and edema associated with thiazolidinedione use. However, a possible physiological role of PPARγ in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPARγ knockout mice. The null mice developed severe polydipsia and polyuria, reduced urine osmolality, and modest hyperphagia. The phenomenon persisted during 3 days of pair feeding and pair drinking, accompanied by progressive weight loss. After 24 h water deprivation, the null mice had a lower urine osmolality, a higher urine volume, a greater weight loss, and a greater rise in hematocrit than the floxed control. Urinary vasopressin (AVP) excretion was not different between the genotypes under basal condition or after WD. The response of urine osmolality to acute and chronic 1-desamino-8-D-arginine vasopressin treatment was attenuated in the null mice, but the total abundance or phosphorylation of aquaporin 2 (AQP2) in the kidney or AVP-induced cAMP production in inner medullary collecting duct suspensions was unaffected. Overall, PPARγ participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response.
Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
Li
L
Zhou
Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
Alexandra
A
Panasiuk
Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
Maicy
M
Downton
Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
Daqiang
D
Zhao
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China.
Baoxue
B
Yang
Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
Zhanjun
Z
Jia
Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and Tianxin.Yang@hsc.utah.edu.
Tianxin
T
Yang
D000818:Animals; D001826:Body Fluids; D004327:Drinking Behavior; D005247:Feeding Behavior; D017353:Gene Deletion; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics*
D047495:PPAR gamma
kidney; peroxisome proliferator-activated receptor; vasopressin