Project description:OBJECTIVE: To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS: ICR mice were food restricted by 50% from gestational days 12.5-18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured. RESULTS: At age 3 weeks, LBW mice with CUG (designated U-C) had body weight comparable with controls (designated C-C); weight was reduced by 49% in LBW mice without CUG (designated U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U mice (P < 0.05 vs. C-C mice). Adipose expression of the lipogenic genes Fasn, AccI, Lpin1, and Srebf1 was significantly increased in U-C compared with both C-C and U-U mice (P < 0.05). Mitochondrial DNA copy number was reduced by >50% in U-C versus U-U mice (P = 0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U mice (P < 0.01). CONCLUSIONS: CUG results in increased adipose tissue lipogenic gene expression and adipocyte diameter but not increased cellularity, suggesting that catch-up fat is primarily associated with lipogenesis rather than adipogenesis in this murine model. Epididymal fat samples were obtained at age 3 weeks from 5 control mice (CC), 5 mice exposed to in utero undernutrition (UC), and 4 mice exposed to undernutrition in utero and during suckling (UU).
Project description:OBJECTIVE: To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS: ICR mice were food restricted by 50% from gestational days 12.5-18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured. RESULTS: At age 3 weeks, LBW mice with CUG (designated U-C) had body weight comparable with controls (designated C-C); weight was reduced by 49% in LBW mice without CUG (designated U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U mice (P < 0.05 vs. C-C mice). Adipose expression of the lipogenic genes Fasn, AccI, Lpin1, and Srebf1 was significantly increased in U-C compared with both C-C and U-U mice (P < 0.05). Mitochondrial DNA copy number was reduced by >50% in U-C versus U-U mice (P = 0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U mice (P < 0.01). CONCLUSIONS: CUG results in increased adipose tissue lipogenic gene expression and adipocyte diameter but not increased cellularity, suggesting that catch-up fat is primarily associated with lipogenesis rather than adipogenesis in this murine model.
Project description:<p>Piglet birth weight is a key determinant of preweaning survival and subsequent growth performance, yet the role of maternal gut microbiota in relation to offspring birth weight in sows remains incompletely characterized. This study aimed to investigate the association between maternal gut microbiota and offspring birth weight in sows. Fecal samples were collected from 260 Landrace × Yorkshire (LY) sows at gestation day 100, and sows were categorized into high birth weight (HBW; 1.41 ± 0.02 kg, 16.25 ± 0.25 piglets/litter, n = 59) and low birth weight (LBW; 1.07 ± 0.02 kg, 12.19 ± 0.22 piglets/litter, n = 52) groups based on the average birth weight of live-born piglets and live litter size. Fecal untargeted metabolomics was performed between groups.</p>
Project description:Low (U) and normal (N) birth weight female porcine offspring were used to study molecular and physiological changes in the liver before and after postnatal feed restriction (R, 50% of controls) and after subsequent refeeding period in comparison to non-restricted control animals (K). Overall, the following questions were addressed at the transcriptional, epigenomic and metabolic level: 1) Are there differences in the hepatic transcriptional profile between U and normal birth weight 2) Are these effects reflected on the metabolic level? 3) Could the possible birth weight-dependent effects be modified through feed restriction intervention? 4) Are these effects persistent and, moreover, can improvements with regard to lipid homeostasis be observed? Microarrays were used to study the effects of birth weight and/or feed restriction on the transcriptional level.
Project description:We explored the hypothesis that gene expression will be dysregulated in the liver of low birth weight (LBW) offspring, distinct from normal birth weight (NBW) offspring, in young adulthood when both birth weight outcomes are challenged with a lifelong postnatal Western diet (WD). Independent of diet, in LBW vs. NBW males, 7 differentially expressed genes (DEGs) were identified, most of which downregulated (5 vs. 2) in LBW males. A similar trend was observed in LBW vs. NBW females, where 12 DEGs were identified, predominantly downregulated in the LBW group (9 vs. 3), irrespective of diet. Lifelong WD consumption exerted a marked influence on liver transcription profiles. Notably, 553 (444 upregulated and 109 downregulated) and 639 (533 upregulated and 106 downregulated) DEGs were identified in males and females, independent of birth weight, respectively. Additionally, in females, birth weight and WD both impacted six genes. Further, transcriptomic analysis revealed 22 (9 upregulated and 13 downregulated) and 55 (12 upregulated and 43 downregulated) DEGs between LBW/WD and NBW/WD groups in males and females, respectively.
Project description:Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the conversion of saturated fatty acids palmitate and stearate to monounsaturated fatty acids palmitoleate and oleate. During adipocyte differentiation, SCD expression increases concomitantly with several transcription factors and lipogenic genes. We used microarrays to examine gene expression in differentiated pre-adipocytes treated with and without an SCD inhibitor. On day 7 of adipocyte differentiation, total RNA was extracted from adipocytes. Two conditions were selected for comparison: total RNA extracted from adipocytes treated with DMSO (control) and or a SCD inhibitor.