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Effect of in utero undernutrition on skeletal muscle gene expression

ABSTRACT: In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood. We have used a mouse model of low birth weight generated through 50% food restriction of mouse dams during the third week of gestation. We have studied in utero food restricted offspring and control offspring that were not food restricted in utero in both the ad libitum and calorie restricted states. Gene expression profiling was performed on tibialis anterior muscle from 8 mice per group, pooled in pairs.

ORGANISM(S): Mus musculus

SUBMITTER: Alexandre Blais

PROVIDER: E-GEOD-53520 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Effect of in utero undernutrition on skeletal muscle gene expression

Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood.

2014-08-01 | GSE53520 | GEO

Intrauterine hyponutrition reduces fetal testosterone production and postnatal sperm count in the C57BL/6N

Project description:There has been growing interest in the relationship between maternal undernutrition and reproductive disorders in male offspring. In the present study, we determined the effects of maternal calorie restriction throughout the critical period for in utero development of the male reproductive system, termed the “masculinization programming window” on the reproductive system of mice. The intratesticular testosterone concentration of the fetuses of calorie-restricted (R) dams was lower than in control fetuses at 17.5 days post coitum. In addition, there was global down-regulation of genes encoding steroidogenic enzymes and a low sperm count in the offspring of R dams (R-offspring) at 6 weeks of age. Microarray analysis of the testes of the offspring identified dysregulation of several genes that might explain the derangement in spermatogenesis in the R-offspring. Thus, the present study provides insights into the impact of maternal undernutrition on the male reproductive system in mice. The deleterious effects probably originate in lower androgen exposure during the “masculinization programming window.”

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Accelerated Postnatal Growth Increases Lipogenic Gene Expression and Adipocyte Size in Low-Birth Weight Mice

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).

2010-03-04 | E-GEOD-16083 | biostudies-arrayexpress

Effects of maternal nutrient restriction during pregnancy on the adult offspring longissimus dorsi transcriptome in cattle

Project description:Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. As skeletal muscle is a major metabolic organ, RNAseq was performed on the longissimus dorsi muscles of slaughter-weight adult females that had been exposed to nutrient-restriction in utero.

2022-07-01 | GSE181149 | GEO

Mus musculus

Project description:Effect of in utero undernutrition on skeletal muscle gene expression

| PRJNA232265 | ENA

Primary muscle cells from in-utero undernourished mice

Project description:ICR mice, age 6-8 weeks.(Harlan, Indianapolis, IN, USA). Housed individually with controlled temperature, humidity, and light-dark cycle (0600h – 1800h). Pregnant mice were housed individually with ad libitum access to standard rodent chow (T.2018, Harlan Teklad, Indianapolis, IN, USA). On day 12.5 of pregnancy, dams were randomly assigned to either a control or undernutrition group. In the undernutrition group, food was restricted to 50% that of gestational day -matched controls for the remainder of pregnancy. After delivery, mothers were given ad libitum access to chow and 24 hours after birth, litters were equalized to eight. We studied mice from 2 groups: in utero undernourished offpring (U) and control offspring (C). Primary muscle cells were isolated from the quadriceps of U and C at 3 weeks old. Isolated primary muscle cells were grown on Matrigel coated flasks in low glucose (5.5 mmol/L) Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 20% FBS, 1X antibiotic-antimycotic, 2.5μg/ml gentamycin and 2.5ng/ml basic fibroblast growth factor. When cells reached approximately 90% confluency, they were differentiated in low glucose DMEM supplemented with 2% FBS, 1X antibiotic-antimycotic, and 2.5μg/ml gentamycin. Other cells were cultured overnight in substrate limited medium (glucose and glutamine free DMEM supplemented with 0.5mM glucose, 1mM glutamine, 0.5mM carnitine and 1% (v/v) FBS; pH 7.4).

2019-09-12 | GSE103689 | GEO

Muscle fiber transdifferentiation in an experimental model of respiratory chain myopathy

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2012-10-18 | E-MEXP-3642 | biostudies-arrayexpress

Transcription profiling of mouse heart, brain, and skeletal muscle to determine the rffect of age, calorie restriction and resveratrol on gene expression

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2008-06-18 | E-GEOD-11291 | biostudies-arrayexpress

Characterization of the skeletal muscle proteome in under-nourished old rats

Project description:Therefore, undernutrition is common in the elderly where its prevalence varies from 4 to 10% at home, from 15 to 30% in care homes and reaches 30 to 70% in hospitals de-pending on the diagnostic criteria used [10]. Most of all, aging impairs the ability to adapt to undernutrition leading to severe loss of body weight and muscle [11-14]. In particular, old rats exhibit defective adaptation to long-term 50% dietary restriction initiated at an advanced age, resulting in dramatic body weight loss and deregulation of protein metabolism in terms of nitrogen balance and protein content, especially at skeletal muscle level [12]. Therefore, in elderly patients, undernutrition exacerbates the state of frailty and dependence, greatly increasing the risk of morbidity and mortality [15]. This is even more critical that the world aging population is growing up. Accord-ing to United Nations statistics on the demographic trend in aging population, the proportion of persons aged 65 or over in the world is projected to reach nearly 16% in 2050, compared to 9% in 2019 [16]. Specific studies are needed to better understand the undernutrition-induced skeletal muscle alterations in order to identify new therapeu-tic targets and prevent sarcopenia in the old population

2022-06-09 | PXD032044 | Pride

Proteomics of circadian rhythms in mouse skeletal muscle tissue during time-restricted feeding

Project description:Time-restricted eating is emerging as a promising dietary intervention that prevents cardiometabolic disease; however, the molecular mechanisms remain largely unknown. It is generally thought that time-restricted feeding-as it is known in animal studies-reprograms circadian rhythms in peripheral organs including skeletal muscle. Recent studies reported that peripheral organs entrain to time-restricted feeding in a highly diverse tissue-specific manner, which is indicated by the kinetics of the circadian clock in peripheral organs, transcriptome and metabolome. A discrepancy is found in the circadian coherence between rhythmic transcripts and rhythmic metabolites, suggesting the presence of additional regulation at the proteome level. To explore the landscape of rhythmic proteins in skeletal muscle from time-restricted fed mice, we sampled 50 mouse tibialis anterior muscle tissues from 11-week-old C57BL/6J female mice. These mice had been fed day time-restricted feeding for 3 weeks, during which food was accessible between Zeitgeber time (ZT) 0 h and ZT 12 h. Samples were dissected and snap-frozen in liquid nitrogen every two hours starting from ZT0 of the first day to ZT0 of the third day. This sampling scheme covers two complete day/night cycles and has two biological replicates per time point for a total of 25 time points. Next, we performed mass spectrometry-based parallel accumulation–serial fragmentation combined with data-independent acquisition (diaPASEF) quantitative proteomics to analyze these mouse skeletal muscle tissues. Together, we have generated a dataset that provide insights into circadian rhythms of skeletal muscle under the regulation of time-restricted feeding in mice.

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