title: In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.
abstract: The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Borengasser
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Faske
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Kang
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas; and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas ShankarKartik@uams.edu.
authors.forename: Kartik
authors.initials: K
authors.lastname: Shankar
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D002153:Calorimetry, Indirect; D059305:Diet, High-Fat; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D045726:Metalloproteases; C555711:PARL protein, rat; D020558:GTP Phosphohydrolases; C498811:Opa1 protein, rat
keywords: PGC1α/β; developmental programming; mitochondrial dynamics; mitofusin; pregnancy