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.

Identification of tRNA-derived small RNAs and their potential roles in porcine skeletal muscle with intrauterine growth restriction

“…The highly expressed tsRNAs were mainly involved in the biological process of embryonic development and cell connection, and most significantly enriched pathways were GnRH signaling pathway, insulin signaling pathway, MAPK signaling pathway, melanogenesis, and focal adhesion signaling pathways. The GnRH signaling pathway ( Korpysz and Szalecki, 2019 ), insulin signaling pathway ( Dunlop et al, 2021 ), and MAPK signaling pathway ( Choi et al, 2020 ) have been reported to be associated with IUGR. In addition, differentially expressed tsRNAs in normal-size and IUGR porcine skeletal muscle were mainly enriched in metabolic pathways, Rap1 signaling pathway, endocytosis, mTOR signaling pathway, and AMPK signaling pathway.…”

An Integrated Multi-OMICS Approach Highlights Elevated Non-Esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing

“…Finally, the profiles of neutral lipid species in NEFA-treated BeWo trophoblasts were analyzed via Thin Liquid Chromatography coupled to Flame Ionization Detection (TLC-FID) as previously described [ 66 ]. In brief, collected lipid samples were dried under a gentle stream of N 2 gas and resuspended in 100% chloroform.…”

A Comprehensive Review of Minerals and Vitamins Synergy: Impacts on Childhood and Adolescent Bone Development

“…Its essence lies not only in ensuring longevity and robust bone mass but also in maintaining quality. Intriguingly, medical research has underscored that a staggering 99% of calcium accumulates in the skeletal system, fortifying the foundation of our framework [17], [18]. Nevertheless, the importance of age-appropriate calcium intake must be noticed, as children require distinct levels of supplementation compared to adults and older individuals.…”

“…Furthermore, low calcium content can impact other essential nutrients, such as zinc, affecting its absorption and supplementation [20]. The timing of calcium supplementation in healthy children and infants also emerges as a relevant factor, revealing that it is most beneficial when they become prone to osteoporosis or experience low calcium intake [17]. Surprisingly, studies have suggested that a low calcium diet in rural Gambian children led to higher bone mineralization and density [17].…”

“…A resounding cheer for osteoblastic bone formation in the flourishing years of children and adolescents [29]. Zinc deficiency can damper growth and development processes [17], [18]. So, finding the Goldilocks zone of zinc intake becomes a priority.…”