title: Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes.
abstract: BACKGROUND
  The aim of this study was to establish the underlying mechanisms by which a post-weaning high-fat diet (HFD) accelerates the perinatal programming of kidney injury occurring in the offspring of diabetic mothers.
  
  
  METHODS
  Male mice, offspring of nondiabetic and diabetic dams were fed with normal diet (ND) or HFD from 4 to 20 wk of age. Rat renal proximal tubular cells were used in vitro.
  
  
  RESULTS
  On ND, the offspring of dams with severe maternal diabetes had an intrauterine growth restriction (IUGR) phenotype and developed mild hypertension and evidence of kidney injury in adulthood. Exposing the IUGR offspring to HFD resulted in rapid weight gain, catch-up growth, and later to profound kidney injury with activation of renal TGFβ1 and collagen type IV expression, increased oxidative stress, and enhanced renal lipid deposition, but not systemic hypertension. Given our data, we speculate that HFD or free fatty acids may accelerate the process of perinatal programming of kidney injury, via increased CD36 and fatty acid-binding protein 4 expression, which may target reactive oxygen species, nuclear factor-kappa B, and TGFβ1 signaling in vivo and in vitro.
  
  
  CONCLUSIONS
  Early postnatal exposure to overnutrition with a HFD increases the risk of development of kidney injury, but not hypertension, in IUGR offspring of dams with maternal diabetes.
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Yessoufou
authors.initials: Y
authors.lastname: Aliou
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Min-Chun
authors.initials: MC
authors.lastname: Liao
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Zhao
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Shiao-Ying
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chenier
authors.affiliation: Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School Boston, Boston, Massachusetts.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Ingelfinger
authors.affiliation: Centre de recherche du Centre hospitalier de l'Universite de Montreal (CRCHUM), Universite de Montreal, Montréal, Quebec, Canada.
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D018955:CD36 Antigens / Q000378:metabolism; D016640:Diabetes, Gestational / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000293:injuries / Q000503:physiopathology*; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D051381:Rats; D014886:Weaning
chemical_list: D018955:CD36 Antigens; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins