title: A short-term transition from a high-fat diet to a normal-fat diet before pregnancy exacerbates female mouse offspring obesity.
abstract: OBJECTIVE
  Recent findings have highlighted the detrimental influence of maternal overnutrition and obesity on fetal development and early life development. However, there are no evidence-based guidelines regarding the optimal strategy for dietary intervention before pregnancy.
  
  
  METHODS
  We used a murine model to study whether switching from a high-fat (HF) diet to a normal-fat (NF) diet (H1N group) 1 week before pregnancy could lead to in utero reprogramming of female offspring obesity; comparator groups were offspring given a consistent maternal HF group or NF group until weaning. After weaning, all female offspring were given the HF diet for either 9 or 12 weeks before being killed humanely.
  
  
  RESULTS
  H1N treatment did not result in maternal weight loss before pregnancy. NF offsprings were neither obese nor glucose intolerant during the entire experimental period. H1N offsprings were most obese after the 12-week postweaning HF diet and displayed glucose intolerance earlier than HF offsprings. Our mechanistic study showed reduced adipocyte insulin receptor substrate 1 (IRS1) and hepatic IRS2 expression and increased adipocyte p-Ser(636/639) and p-Ser(612) of H1N or HF offspring compared with that in the NF offspring. Among all groups, the H1N offspring had lowest level of IRS1 and the highest levels of p-Ser(636/639) and p-Ser(612) in gonadal adipocyte. In addition, the H1N offspring further reduced the expression of Glut4 and Glut2, vs those of the HF offspring, which was lower compared with the NF offspring. There were also enhanced expression of genes inhibiting glycogenesis and decreased hepatic glycogen in H1N vs HF or NF offspring. Furthermore, we showed extremely higher expression of lipogenesis and adipogenesis genes in gonadal adipocytes of H1N offspring compared with all other groups.
  
  
  CONCLUSIONS
  Our results suggest that a transition from an HF diet to an NF diet shortly before pregnancy, without resulting in maternal weight loss, is not necessarily beneficial and may have deleterious effects on offspring.
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.|Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.
authors.forename: P
authors.initials: P
authors.lastname: Olson
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rasmussen
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.
authors.forename: B
authors.initials: B
authors.lastname: Keith
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.
authors.forename: M
authors.initials: M
authors.lastname: Williamson
authors.affiliation: Department of Pathology, University of North Dakota, Grand Forks, ND, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Zhang
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA.|Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000473:pathology; D039401:Prenatal Nutritional Physiological Phenomena / Q000187:drug effects*; D014886:Weaning
chemical_list: D004041:Dietary Fats