Key points
Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood.
We developed a rat model of diet‐induced gestational diabetes ...mellitus that recapitulates many of the clinical features of the disease, including excessive gestational weight gain, glucose intolerance, hyperinsulinaemia and mild hyperglycaemia.
Compared to the offspring of lean dams, exposure to gestational diabetes mellitus during the prenatal period resulted in obesity, hepatic steatosis and insulin resistance in young rat offspring that consumed a postnatal diet that was low in fat.
The combination of maternal gestational diabetes mellitus and the postnatal consumption of a high‐fat diet by the offspring caused a more severe metabolic phenotype.
Metabolomic profiling of the liver tissues of the offspring of gestational diabetic dams revealed accumulation of lipotoxic lipids and reduced phosphatidylethanolamine levels compared to the offspring of lean dams.
The results establish that gestational diabetes mellitus is a driver of hepatic steatosis and insulin resistance in the offspring.
Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague‐Dawley rats were fed a high‐fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low‐fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor‐α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.
As an emerging platform technology, metabolomics offers new insights into the pathomechanisms associated with complex disease conditions, including cardiovascular diseases. It also facilitates ...assessing the risk of developing the disease before its clinical manifestation. For this reason, metabolomics is of growing interest for understanding the pathogenesis of acute coronary syndromes (ACS), finding new biomarkers of ACS, and its associated risk management. Metabolomics-based studies in ACS have already demonstrated immense potential for biomarker discovery and mechanistic insights by identifying metabolomic signatures (e.g., branched-chain amino acids, acylcarnitines, lysophosphatidylcholines) associated with disease progression. Herein, we discuss the various metabolomics approaches and the challenges involved in metabolic profiling, focusing on ACS. Special attention has been paid to the clinical studies of metabolomics and lipidomics in ACS, with an emphasis on ischemia/reperfusion injury.
Introduction
Although pulses are nutritious foods containing high amounts of protein, fiber and phytochemicals, their consumption and use in the food industry have been limited due to the formation ...of unappealing flavors/aromas described as beany, green, and grassy. Lipoxygenase (LOX) enzymes are prevalent among pulse seeds, and their activity can lead to the formation of specific volatile organic compounds (VOCs) from certain polyunsaturated fatty acids (PUFAs). As a widespread issue in legumes, including soybean, these VOCs have been linked to certain unappealing taste perception of foods containing processed pulse seeds.
Methods
To address this problem in pea and as proof of principle to promote the wider use of pulses, a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) construct was designed to create null alleles (knockouts) of
PsLOX2
which had been implicated in the generation of VOCs in peas.
Results and discussion
Successful CRISPR/Cas9-mediated LOX gene editing of stable transgenic pea lines (TGP) was confirmed by DNA sequencing of the wild type (WT) and TGP
pslox2
mutant lines. These lines were also assessed for LOX activity, PUFA levels, and VOCs. Compared to WT peas, the TGP lines showed a significant reduction (p < 0.05) in LOX activity and in the concentration of key VOCs, including hexanal, 2-hexenal, heptanal, (E)-2-heptenal, (E,E)-2,4-heptadienal, 1-octen-3-ol, octanal, (E)-2-octenal (E,E)-2,4-nonadienal and furan-2-pentyl. The content of two essential PUFAs, linoleic and α-linolenic acids, the known substrates of LOX in plants, was higher in TGP flours, indicating the efficacy of the CRISPR-mediated gene editing in minimizing their oxidation and the further modification of PUFAs and their products. The collection of VOCs from the headspace of ground pea seeds, using a portable eNose also distinguished the TGP and WT lines. Multiple regression analysis showed that LOX activity correlated with the two VOCs, heptanal and (E,E)-2,4-heptadienal in pea flours. Partial Least Squares Regression (PLS-R) plot for selected PUFAs, VOCs, and sensor responses in WT and TGP lines showed distinct clusters for WT and TGP lines. Together this data demonstrates the utility of CRISPR mediated mutagenesis of
PsLOX2
to quickly improve aroma and fatty acid (FA) profiles of pea seeds of an elite Canadian variety.
The current study was designed to assess the fatty acid composition and sensory attributes of eggs procured from hens consuming diets containing canola meal (CM) and/or flax oil (FO). A total of 96 ...group-caged White Lohmann hens received 1 of 4 isonitrogenous and isoenergetic diets for a period of 4 weeks. Diets were arranged in a 2 × 2 factorial design, containing 24% canola meal, 7.5% flax oil, both, or neither (control). All yolk fatty acids were affected by flax oil inclusion, with the exception of stearic acid (SA) and docosapentaenoic acid (DPA). Only SA was affected by CM inclusion. Additionally, significant interactions between CM and FO were observed for linoleic acid (LA) and total omega-6 polyunsaturated fatty acids (PUFA), with DPA approaching significance (P = 0.069). Trained panelists (n = 8) evaluated 7 aroma (‘egg’, ‘creamy’, ‘buttery’, ‘salty’, ‘sweet’, ‘barny’, and ‘oceanic’) and 6 flavor (‘egg’, ‘creamy’, ‘buttery’, ‘salty’, ‘brothy’, and ‘oceanic’) attributes of cooked egg product. No significant differences (P > 0.05) in aroma attributes were found between eggs from different dietary treatments. However, egg, creamy, buttery, and oceanic flavors were significantly different between the dietary treatments (P < 0.05). While oceanic flavor significantly increased with inclusion of FO, egg and creamy flavors showed a significant decrease (P < 0.05). Although CM addition alone did not result in significant sensory changes, the pairing of CM and FO resulted in even greater sensory changes than using FO alone, specifically with regard to egg flavor. Results from partial least squares analyses showed a strong association between oceanic flavor and omega-3 PUFA. Oppositely, egg, creamy, and buttery flavors were more correlated with the presence of omega-6 PUFA and palmitic acid. This experiment provides evidence that the interaction between CM and FO in the White Lohmann hen diet results in sensory changes of cooked eggs associated in part with changes in yolk fatty acid content.
The formation of ATP breakdown products in chicken M. pectoralis major post-slaughter is reported. The concentrations of metabolites were followed in chicken breast throughout the carcass processing ...post-slaughter and during chilled storage. The concentration of glucose remains similar throughout the period whilst that of glucose-6-phosphate decreases linearly. Glucose and glucose-6-phosphate concentrations were inversely related to the pHu of the breast meat throughout chilled storage. Rapid post-mortem glycolysis and high pHu values suggest the occurrence of stress at and pre-slaughter. Whilst ATP, ADP and AMP were rapidly broken down, the concentration of IMP rose rapidly and remained high. Concentrations of inosine, ribose and hypoxanthine increased gradually post-slaughter but an initial increase in ribose phosphate was not sustained. Most of the potential ribose present in chicken meat, believed to be important for flavor formation, remains bound in the form of inosine and IMP. There is evidence that additional breakdown pathways for ribose and ribose-5-phosphate may deplete the concentrations of these precursors.
► ATP breakdown products and glucose were monitored in chicken post-slaughter. ► ATP, ADP and AMP were rapidly broken down while IMP increased rapidly. ► Glucose and G6P were inversely related to the pHu of the breast meat. ► Most ribose, an important flavor precursor, remains bound in inosine and IMP.
Diabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated ...protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes. We hypothesized that sub-optimal insulin-like growth factor 1 (IGF-1) signaling in diabetes drives loss of AMPK activity and mitochondrial function, both contributing to development of DSPN.
Age-matched control Sprague-Dawley rats and streptozotocin (STZ)-induced type 1 diabetic rats with/without IGF-1 therapy were used for in vivo studies. For in vitro studies, DRG neurons from control and STZ-diabetic rats were cultured and treated with/without IGF-1 in the presence or absence of inhibitors or siRNAs.
Dysregulation of mRNAs for IGF-1, AMPKα2, ATP5a1 (subunit of ATPase), and PGC-1β occurred in DRG of diabetic vs. control rats. IGF-1 up-regulated mRNA levels of these genes in cultured DRGs from control or diabetic rats. IGF-1 treatment of DRG cultures significantly (P < 0.05) increased phosphorylation of Akt, P70S6K, AMPK and acetyl-CoA carboxylase (ACC). Mitochondrial gene expression and oxygen consumption rate (spare respiratory capacity), ATP production, mtDNA/nDNA ratio and neurite outgrowth were augmented (P < 0.05). AMPK inhibitor, Compound C, or AMPKα1-specific siRNA suppressed IGF-1 elevation of mitochondrial function, mtDNA and neurite outgrowth. Diabetic rats treated with IGF-1 exhibited reversal of thermal hypoalgesia and, in a separate study, reversed the deficit in corneal nerve profiles. In diabetic rats, IGF-1 elevated the levels of AMPK and P70S6K phosphorylation, raised Complex IV-MTCO1 and Complex V-ATP5a protein expression, and restored the enzyme activities of Complex IV and I in the DRG. IGF-1 prevented TCA metabolite build-up in nerve.
In DRG neuron cultures IGF-1 signals via AMPK to elevate mitochondrial function and drive axonal outgrowth. We propose that this signaling axis mediates IGF-1-dependent protection from distal dying-back of fibers in diabetic neuropathy.
•IGF-1 activates AMPK to drive mitochondrial phenotype in sensory neurons.•AMPK isoforms differentially regulate mitochondrial gene expression and respiratory activity.•IGF-1 treatment of type 1 diabetic rodents protected from neuropathy.•DRG of diabetic rats treated with IGF-1 exhibited raised activity and gene expression of AMPK and respiratory complexes.
Fatty acids come in a variety of structures and, because of this, create a variety of functions for these lipids. Some fatty acids have a role to play in energy metabolism, some help in lipid ...storage, cell structure, the physical state of the lipid, and even in food stability. Fatty acid metabolism plays a particularly important role in meeting the energy demands of the heart. It is the primary source of myocardial energy in control conditions. Its role changes dramatically in disease states in the heart, but the pathologic role these fatty acids play depends upon the type of cardiovascular disease and the type of fatty acid. However, no matter how good a food is for one's health, its taste will ultimately become a deciding factor in its influence on human health. No food will provide health benefits if it is not ingested. This review discusses the taste characteristics of culinary oils that contain fatty acids and how these fatty acids affect the performance of the heart during healthy and diseased conditions. The contrasting contributions that different fatty acid molecules have in either promoting cardiac pathologies or protecting the heart from cardiovascular disease is also highlighted in this article.
•Short-chain chicken skin peptides had better ACE inhibition than long-chain peptides.•Kinetics of ACE and renin inhibition showed mainly mixed-type mechanism.•The hydrolysates had the strongest ...blood pressure-lowering effect in spontaneously hypertensive rats.•Blood pressure-lowering effect contrasted with observed in vitro ACE inhibition.•In vitro renin inhibition was consistent with blood pressure-lowering effect.
Chicken skin protein hydrolysates (CSPHs) and their membrane ultrafiltration fractions were investigated for their blood pressure lowering effects. Chicken skins from thigh or breast muscles were hydrolyzed with 3% Alcalase or 1% pepsin/pancreatin, respectively; hydrolysates were then fractionated into <1, 1–3, 3–5, and 5–10 kDa peptide sizes. Chicken breast skin hydrolysate (CBSH) and peptide fractions inhibited angiotensin converting enzyme (ACE) with IC50 values of 0.36–0.64 mg/mL, which were significantly (p < 0.05) higher than the 0.42–0.75 mg/mL values obtained for chicken thigh skin hydrolysate (CTSH) and peptide fractions. Results suggest that a high content of branched-chain amino acids contributed to the significantly (p < 0.05) higher ACE-inhibition by <1 kDa peptide fraction. All the samples with exception of the CBSH 3 kDa fraction had similar renin inhibitory values. Kinetics studies revealed that enzyme inhibition pattern was mostly of the mixed-type for ACE and renin. Oral administration of 100 mg peptides/kg body weight to spontaneously hypertensive rats led to maximum systolic blood pressure reduction of −32.67 and −31.33 mmHg after 6 h for CTSH and CBSH, respectively. We conclude that the CSPHs have potential use as active ingredients to formulate antihypertensive functional foods and nutraceuticals.
Pyridoxal 5′-phosphate (PLP; a B6 vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to ...cysteine. While overt vitamin B6 deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B6 deficiency and a study was conducted to examine the in vivo effect of 1-amino d-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B6 deficient rats. Male weaning rats received a semi-purified diet containing either 7mg/kg (control; CD) or 0.7mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10mg/kg diet for 5weeks. Perturbations in vitamin B6 biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine β-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B6 deficient.
Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic ...biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
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