title: Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.
abstract: The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Svensson
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland.
authors.forename: Svenia
authors.initials: S
authors.lastname: Schnyder
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Cardel
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0003-0603-1097
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D007674:Kidney Diseases / Q000378:metabolism* / Q000652:urine; D007684:Kidney Tubules / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012964:Sodium / Q000652:urine*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012964:Sodium