Biology subjects

Ampong, I.

Publications and source records attributed to Ampong, I..

3 recordsLinked to original sources

bioRxiv2023

Multi-omics Analysis of Aging Liver Reveals Changes in Endoplasmic Stress and Degradation Pathways in Female Nonhuman Primates

The liver is critical for functions that support metabolism, immunity, digestion, detoxification, and vitamin storage. Aging is associated with severity and poor prognosis of various liver diseases such as nonalcoholic fatty liver disease (NAFLD). Previous studies have used multi-omic approaches to study liver diseases or to examine the effects of aging on the liver. However, to date, no studies have used an integrated omics approach to investigate aging-associated molecular changes in the livers of healthy female nonhuman primates. The goal of this study was to identify molecular changes associated with healthy aging in the livers of female baboons (Papio sp., n=35) by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. To integrate omics data, we performed unbiased weighted gene co-expression network analysis (WGCNA), and the results revealed 3 modules containing 3,149 genes and 33 proteins were positively correlated with age, and 2 modules containing 37 genes and 216 proteins were negatively correlated with age. Pathway enrichment analysis showed that unfolded protein response (UPR) and endoplasmic reticulum (ER) stress were positively associated with age, whereas xenobiotic metabolism and melatonin and serotonin degradation pathways were negatively associated with age. The findings of our study suggest that UPR and a reduction in reactive oxygen species generated from serotonin degradation could protect the liver from oxidative stress during the aging process in healthy female baboons.

molecular biology↗

bioRxiv2022

Integrated Multi-Omics Analysis of Brain Aging in Female Nonhuman Primates Reveals Altered Signaling Pathways Relevant to Age-Related Disorders

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis (WGCNA) to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found GABA tissue content associated with these signaling pathways, providing one potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

systems biology↗

bioRxiv2022

Regulation of odd chain fatty acid metabolism in the development of metabolic diseases in mice fed a low protein diet.

Nonalcoholic fatty liver disease (NAFLD) and Metabolic syndrome (MS) have become a global health concern as incidence of these metabolic disorders is growing rapidly in developing countries particularly in the Middle East, South America and Africa. Studies have shown that protein restriction is associated with increased risk of metabolic diseases, possibly through effects on fatty acid (FA) metabolism. In the present study, we investigated whether a low protein diet modulates FA metabolism and whether methyl donor supplementation can ameliorate these effects and improve metabolic health. Male C57BL/6 mice were fed either a low protein diet (LPD, 90 g/kg protein, n=8), a LPD supplemented with methyl donors (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12, n=8) or normal protein diet (NPD, 180 g/kg protein, n=8) for 7 weeks prior to analysis of serum fatty acid profiles by GC FID and MS and liver fatty acid synthesis and uptake gene expression by RT-qPCR. We observed significant depletion of serum C15:0 and C17:0 in LPD-fed males compared to NPD. Serum long chain saturated FAs C18:0 and C24:0 were increased in LPD male mice compared to NPD. Gene expression analysis revealed an upregulation of hepatic cluster of differentiation 36 (CD36) expression in LPD mice compared to NPD suggesting increased fat uptake in the liver. However, when LPD diet was supplemented with methyl donors, we observed either no change in serum C15: 0 and an increased serum C17:0 compared to LPD with no methyl donor supplementation. Again, methyl donor supplementation upregulated fatty acid desaturase 1 (FADS1), thioredoxin-1 (TRX1) and catalase (CAT) expression in the liver of MD-LPD fed mice compared to LPD mice. Altogether, our study revealed that odd chain fatty acids (OCFA)s are key early markers observed in a suboptimal diet-induced metabolic changes and may be potential targets to improve metabolic health outcomes.

biochemistry↗