title: Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice.
abstract: OBJECTIVE
  The aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma by Bezafibrate (BZ) could attenuate hepatic and white adipose tissue (WAT) abnormalities in male offspring from diet-induced obese dams.
  
  
  METHODS
  C57BL/6 female mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF; 49% lipids) diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet) started at 12 weeks of age and was maintained for three weeks.
  
  
  RESULTS
  The HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1) in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat.
  
  
  CONCLUSIONS
  Diet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: D'Angelo Carlo
authors.initials: DC
authors.lastname: Magliano
authors.forename: Thereza Cristina Lonzetti
authors.initials: TC
authors.lastname: Bargut
authors.forename: Simone Nunes
authors.initials: SN
authors.lastname: de Carvalho
authors.forename: Marcia Barbosa
authors.initials: MB
authors.lastname: Aguila
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D017667:Adipocytes / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D050260:Carbohydrate Metabolism; D048429:Cell Size; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D002149:Energy Intake; D004734:Energy Metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology; D005260:Female; D015870:Gene Expression; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000209:etiology; D039401:Prenatal Nutritional Physiological Phenomena; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D001629:Bezafibrate