Systemic PPAR gamma deletion causes severe disturbance in fluid homeostasis in mice

Zhou L, Panasiuk A, Downton M, Zhao D, Yang B, Jia Z, Yang T. Systemic PPAR gamma deletion causes severe disturbance in fluid homeostasis in mice. Physiol Genomics 47: 541-547, 2015. First published September 1, 2015; doi:10.1152/physiolgenomics.00066.2015.-The pharmacological action of peroxisome proliferator-activated receptor (PPAR)gamma 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 PPAR gamma in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPAR gamma 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, PPAR gamma participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response.National Natural Science Foundation of China [91439205, 31330037]; National National Institute of Diabetes and Digestive and Kidney Diseases [DK-094956, DK-104072]; National Basic Research Program of China 973 Program [2012CB517600, 2012CB517602]; China Postdoctoral Science Foundation; VA Merit ReviewSCI(E)PubMedARTICLETianxin.Yang@hsc.utah.edu11541-5474