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Differential and Synergistic Effects of Low Birth Weight and Western Diet on Skeletal Muscle Vasculature, Mitochondrial Lipid Metabolism and Insulin Signaling in Male Guinea Pigs.

ABSTRACT: 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.

SUBMITTER: Dunlop K

PROVIDER: S-EPMC8704817 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Differential and Synergistic Effects of Low Birth Weight and Western Diet on Skeletal Muscle Vasculature, Mitochondrial Lipid Metabolism and Insulin Signaling in Male Guinea Pigs.

Dunlop Kristyn K Sarr Ousseynou O Stachura Nicole N Zhao Lin L Nygard Karen K Thompson Jennifer A JA Hadway Jennifer J Richardson Bryan S BS Bureau Yves Y Borradaile Nica N Lee Ting-Yim TY Regnault Timothy R H TRH

Nutrients 20211129 12

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/LB ...[more]

PMID: 34959870

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Project description:BackgroundThe gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse in utero environment such as placental insufficiency resulting in low birth weight (LBW) offspring, contributes to an increased risk of metabolic diseases such as fatty liver infiltration and liver dysfunction in later life. We sought to understand the potential interactive effects of exposure to a WD upon growing LBW offspring. We postulated that LBW offspring when challenged with a poor postnatal diet, would display an altered microbiota and more severe liver metabolic dysfunction.MethodsThe fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed.ResultsThe life-long consumption of WD following weaning into young adulthood resulted in increased total cholesterol, triglycerides and alanine aminotransferase levels in association with an altered GIT microbiota when compared to offspring consuming CD. Neither birth weight nor sex were associated with any significant changes in microbiota alpha diversity, by measuring the Shannon's diversity index. One hundred forty-eight operational taxonomic units were statistically distinct between the diet groups, independent of birth weight. In the WD group, significant decreases were detected in Barnesiella, Methanobrevibacter smithii and relatives of Oscillospira guillermondii, while Butyricimonas and Bacteroides spp. were increased.DiscussionThese results describe the GIT microbiota in a guinea pig model of LBW and WD associated metabolic syndrome and highlight several WD specific GIT alterations associated with human metabolic disease.

Project description:In commercial pig farming, an increasing number of low birth weight (LBW) piglets are born, due to selection for large litter sizes. While LBW piglets have a higher risk of pre-weaning mortality, a considerable number of these piglets survive to slaughter age. In humans, LBW is a risk factor for long-term cognitive impairments. In pigs, studies examining the post-weaning effects of LBW on cognition have reported contradictory results. Therefore, the current study aimed to assess the effects of LBW on cognitive development in pigs using an improved study design, by (1) testing a larger sample size than previous studies, (2) assessing acute and chronic stress responses to account for a potential altered stress response in LBW pigs, and (3) testing both female and male pigs to account for potential confounding effects of sex. Learning and memory of 20 LBW pigs and 20 normal birth weight (NBW) pigs, both groups consisting of 10 females and 10 males, were compared using a spatial holeboard task. In this task, pigs had to learn and remember the locations of hidden food rewards. After a pig had successfully acquired the task, it was presented with two successive reversal phases during which it was presented with a new configuration of reward locations. The holeboard allows for simultaneous assessment of working and reference memory, as well as measures of motivation, exploration, and behavioral flexibility. Mixed model ANOVAs revealed a transiently impaired reference memory performance of LBW pigs, implying they had more difficulty learning their reward configuration in the holeboard. Also, LBW piglets showed increased pre-weaning hair cortisol concentrations compared to their NBW siblings. No other effects of LBW were found. Sex had no direct or interaction effects on any measures of holeboard performance or stress. It is possible that the enriched housing conditions applied during our study had an ameliorating effect on our pigs' cognitive development. Overall, our results suggest LBW has a negative effect on post-weaning cognitive performance in pigs. This could have welfare consequences as cognitive skills are required for pigs to learn how to correctly respond to their environment.

Project description:BackgroundCarotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity.MethodsAdult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour-1) for 8 h.day-1 for 12 consecutive days.FindingsCIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls.InterpretationIncreased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing.FundingThe Department of Physiology, and APC Microbiome Ireland, UCC.

Dataset Information

Differential and Synergistic Effects of Low Birth Weight and Western Diet on Skeletal Muscle Vasculature, Mitochondrial Lipid Metabolism and Insulin Signaling in Male Guinea Pigs.

Publications

Differential and Synergistic Effects of Low Birth Weight and Western Diet on Skeletal Muscle Vasculature, Mitochondrial Lipid Metabolism and Insulin Signaling in Male Guinea Pigs.

Similar Datasets

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