Western diet consumption through early life induces microvesicular hepatic steatosis in association with an altered metabolome in low birth weight Guinea pigs

Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload.

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The Role of Maternal Early-Life and Later-Life Risk Factors on Offspring Low Birth Weight: Findings From a Three-Generational Study

Journal of Adolescent Health ◽

10.1016/j.jadohealth.2010.11.246 ◽

2011 ◽

Vol 49 (2) ◽

pp. 166-171 ◽

Cited By ~ 37

Author(s):

Amelia R. Gavin ◽

Karl G. Hill ◽

J. David Hawkins ◽

Carl Maas

Keyword(s):

Risk Factors ◽

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Later Life ◽

Generational Study

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Birth weight influences the kidney size and function of Bangladeshi children

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000976 ◽

2017 ◽

Vol 9 (4) ◽

pp. 386-394 ◽

Cited By ~ 4

Author(s):

F. Ferdous ◽

E. Ma ◽

R. Raqib ◽

Y. Wagatsuma

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Kidney Volume ◽

Normal Birth Weight ◽

Kidney Size ◽

Normal Birth ◽

Life Conditions ◽

Early Life Conditions ◽

And Function

Early-life conditions influence organ growth patterns and their functions, as well as subsequent risk for non-communicable chronic diseases in later life. A limited number of studies have determined that in Bangladesh, kidney size relates to its function among children as a consequence of the maternal and postnatal conditions. The present study objectives were to determine early-life conditions in relation to childhood kidney size and to compare their influences on kidney function. The study was embedded in a population-based prospective cohort of 1067 full-term singleton live births followed from fetal life onward. Kidney volume was measured by ultrasound in children at the age of 4.5 years (range 45–64 months), and the estimated glomerular filtration rate (eGFR) was assessed at the age of 9 years (range 96–116 months). The mean (s.d.) kidney volume of children at 4.5 years was 64.2 (11.3) cm3, with a significant mean difference observed between low birth weight and normal birth weight children (P<0.001). The multivariable model showed, changes in status from low birth weight to normal birth weight children, with kidney volume increases of 2.92 cm3/m2, after adjusting for the child’s age, sex, maternal age and early pregnancy body mass index, and socio-economic index variables. One-unit change in kidney volume (cm3/m2) improved the eGFR to 0.18 ml/min/1.73 m2. The eGFR in low birth weight children was 5.44 ml/min/1.73 m2 less than that in normal birth weight children after adjustments. Low birth weight leads to adverse effects on kidney size and function in children.

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Early Life Microcirculatory Plasticity and Blood Pressure Changes in Low Birth Weight Infants Born to Normotensive Mothers: A Cohort Study

American Journal of Hypertension ◽

10.1093/ajh/hpz034 ◽

2019 ◽

Vol 32 (6) ◽

pp. 570-578 ◽

Cited By ~ 1

Author(s):

Muti Goloba ◽

Rajendra Raghuraman ◽

Nansi Botros ◽

Uzma Khan ◽

Monique Klein ◽

...

Keyword(s):

Blood Pressure ◽

Cohort Study ◽

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Low Birth Weight Infants ◽

Pressure Changes

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Sex-specific alterations in hepatic cholesterol metabolism in low birth weight adult guinea pigs

Pediatric Research ◽

10.1038/s41390-021-01491-w ◽

2021 ◽

Author(s):

Ousseynou Sarr ◽

Katherine E. Mathers ◽

Christina Vanderboor ◽

Kristina Wiggers ◽

Aditya Devgan ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Guinea Pigs ◽

Cholesterol Metabolism ◽

Hepatic Cholesterol

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Impact of early life nutrition on growth and intestinal microflora composition in low-birth-weight infants

Näringsforskning ◽

10.3402/fnr.v41i0.1750 ◽

1997 ◽

Vol 41 (1) ◽

pp. 71-74

Author(s):

Anne Ormisson ◽

Epp Sepp ◽

Urmas Siigur ◽

Heili Varendi ◽

Marika Mikelsaar

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Intestinal Microflora ◽

Low Birth Weight Infants

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Sex-specific Alterations in Hepatic Cholesterol Metabolism in Young Uteroplacental Insufficiency-induced Low Birth Weight Adult Guinea Pig Offspring

10.1101/2020.11.12.379891 ◽

2020 ◽

Author(s):

Ousseynou Sarr ◽

Katherine E. Mathers ◽

Christina Vanderboor ◽

Aditya Devgan ◽

Daniel B. Hardy ◽

...

Keyword(s):

Risk Factor ◽

Birth Weight ◽

Young Adult ◽

Low Birth Weight ◽

Guinea Pig ◽

Guinea Pigs ◽

Cholesterol Metabolism ◽

Later Life ◽

Male Offspring ◽

Hepatic Cholesterol

AbstractBackgroundIntrauterine growth restriction (IUGR) and low birth weight (LBW) have been widely reported as an independent risk factor for hypercholesterolemia and increased hepatic cholesterol underlying liver dysfunction in adulthood. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.MethodsHepatic cholesterol metabolism pathways were studied in uterine artery ablation-induced LBW and normal birth weight (NBW) male and female guinea pig offspring at postnatal day 150.ResultsHepatic free and total cholesterol were increased in LBW versus NBW males. Transcriptome analysis of LBW versus NBW livers revealed that “Cholesterol metabolism” was an enriched pathway in LBW males but not females. Microsomal triglyceride transfer protein and cytochrome P450 7A1 protein, involved in hepatic cholesterol efflux and catabolism, respectively, and catalase activity were decreased in LBW male livers. Superoxide dismutase activity was reduced in LBW males but increased in LBW females.ConclusionsUPI environment is associated with a later life programed hepatic cholesterol accumulation via impaired cholesterol elimination, in a sex-specific manner. These programmed alterations could underlie later life cholesterol-induced hepatic lipotoxicity in LBW male offspring.Impact StatementLow birth weight (LBW) is a risk factor for adult hypercholesterolemia and increased hepatic cholesterol.Uteroplacental insufficiency (UPI) resulting in LBW increased hepatic cholesterol content, altered hepatic expression of cholesterol metabolism-related genes in young adult guinea pigs.UPI-induced LBW was also associated with markers of a compromised hepatic cholesterol elimination process and failing antioxidant system in young adult guinea pigs.These changes, at the current age studied, were sex-specific, only being observed in LBW males and not LBW females.These programmed alterations could lead to further hepatic damage and greater predisposition to liver diseases in UPI-induced LBW male offspring as they age.

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