Biology subjects

Comuzzie, A. G.

Publications and source records attributed to Comuzzie, A. G..

3 recordsLinked to original sources

bioRxiv2023

Maternal Under-Nutrition During Pregnancy Alters the Molecular Response to Over-Nutrition in Multiple Organs and Tissues in Juvenile Offspring

Previous studies suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We examined whether NHP juvenile offspring of pregnancies with maternal undernutrition (MUN) had altered response to a high-fat, high-carbohydrate diet plus sugar drink challenge (HFCS) compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation, and weaned offspring fed chow diet ad libitum. Offspring of MUN were growth restricted at birth. At [~]4.5y offspring received a 7-week HFCS challenge. Baseline and HFCS gene expression in liver, omental fat, and skeletal muscle, liver glycogen content, and fat cell size were quantified. MUN offspring had lower BMI and liver glycogen compared with CON. Pathway analysis showed differences for skeletal muscle and liver, including hepatic splicing and unfolded protein response. MUN offspring consumed more sugar drink than CON. After HFCS, MUN BMIs were similar to CON. Liver showed coordinated response to HFCS in CON but not MUN. Pathway and liver glycogen differences between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin concentrations, omental adipocyte cell size, liver glycogen content, and tissue-specific molecular response to HFCS challenge suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet. O_FIG O_LINKSMALLFIG WIDTH=172 HEIGHT=200 SRC="FIGDIR/small/548121v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@b15085org.highwire.dtl.DTLVardef@11d4c1dorg.highwire.dtl.DTLVardef@704209org.highwire.dtl.DTLVardef@1ff9791_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2019

Metabolic Reprogramming: Short-term Western Diet Exposure Induces Sustained Changes in Plasma Metabolites

Dietary patterns are well known to contribute to the metabolic syndrome and related disorders. We evaluated the impact of a short-term Westernized diet (WD) exposure on systemic plasma metabolomic changes in a cohort of adult male baboons. In this pilot study, five male baboons (n=5) raised and maintained on a standard monkey chow diet (high complex carbohydrates, low fat) were exposed to a challenge WD (high in saturated fats and simple carbohydrates) for 7 weeks (49 d), followed by a 57-day washout period on monkey chow (106 d). In addition to monitoring clinical measures, we used a comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (2D GC-ToF-MS) platform to assess the metabolomic changes in plasma at three time points. Twenty-three metabolites were changed in response to the WD (49 d), but the response across the animals was highly variable. All animals presented a very different metabolic profile than at baseline (0 d), and the washout period resulted in a relatively homogenous metabolic state across all animals. A short-term exposure to a WD led to long-term changes in the metabolic profile, suggesting a "reset" of the metabolic program.

systems biology↗

bioRxiv2017

Assessment of DNA methylation patterns in the bone and cartilage of a nonhuman primate model of osteoarthritis

ObjectiveOsteoarthritis (OA) impacts humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA.\n\nDesignTrabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, five with and five without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues.\n\nResultsApproximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the two filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues.\n\nConclusionsOverall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.

genetics↗