title: [Influence of high-fat diet in paternal C57BL/6 mice on liver fat deposition in offspring].
abstract: Objective:To investigate the influence of high-fat diet (HFD) in paternal C57BL/6 mice on HFD-induced liver fat deposition in male offspring, as well as transgenerational inheritance caused by paternal HFD and related mechanisms.Methods:A total of 20 male C57BL/6 mice aged 3 weeks (F0) were randomly divided into normal control group (C, 10 mice) and HFD group (HF, 10 mice). After 12 weeks of HFD intervention, the male mice in the HFD group mated with female ones treated with normal diet and pups were obtained. Male pups (F1) were selected as study subjects. According to the intervention for F0 mice, male F1 mice were divided into control male offspring group (CM, 8 mice) and HFD male offspring group (HFM, 9 mice). All these mice were given normal diet after weaning until 4 weeks old, followed by HFD for 4 weeks. The body length and body weight were measured and recorded every week. Oil red O staining was used to observe fat deposition in the liver. Western blot and real-time PCR were used to measure the expression of related proteins and genes involved in the de novo synthesis and aerobic oxidation of fatty acid, mitochondriogenesis, and autophagy.Results:After 4 weeks of HFD intervention, the HFM group had a significantly higher body weight than the CM group (P< 0.05); the oil red O staining showed that compared with the CM group, the HFM had a significant increase in liver fat deposition and a significantly higher integral absorbance value in the oil red O staining-positive area (384 360±57 600 vs 236 754±12 607,P< 0.01). For related factors involved in the de novo synthesis of fatty acid in the liver, compared with the CM group, the HFM group had significant increases in the expression of sterol regulatory element-binding protein-1 and fatty acid synthase (P< 0.05); for related factors involved in the mitochondrial biosynthesis in the liver, the HFM group had significant reductions in the relative expression of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1, and mitochondrial transcription factor A compared with the CM group (P< 0.05). For autophagy-related factors in the liver in the F1 mice, compared with the CM group, the HFM group had a significant reduction in microtubule-associated protein I light chain 3 (LC3-II/I) (P< 0.05) and a significant increase in P62 (P< 0.05), suggesting a reduced autophagy function in the liver.Conclusion:HFD intervention for paternal C57BL/6 mice can increase HFD-induced liver fat deposition in male offspring, which may be related to the increased de novo synthesis of fatty acid and reduced mitochondriogenesis and autophagy function in the liver.
authors.affiliation: Department of Endocrinology of the Third Central Hospital, Tianjin Key Laboratory of Artificial Cells, Tianjin 300170, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Tianjin Medical University, Tianjin 300070, China.
authors.forename: H G
authors.initials: HG
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Tianjin Medical University, Tianjin 300070, China.
authors.forename: L
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Endocrinology of the Third Central Hospital, Tianjin Key Laboratory of Artificial Cells, Tianjin 300170, China.
authors.forename: F S
authors.initials: FS
authors.lastname: Di
mesh_terms: D000818:Animals; D001835:Body Weight; D004268:DNA-Binding Proteins / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C422562:mitochondrial transcription factor A
keywords: Fatty liver; Male pup; Paternal obesity