Metabolic Imprinting Research Articles

Bacterial Catabolism of Phthalates With Estrogenic Activity Used as Plasticisers in the Manufacture of Plastic Products.

Phthalic acid esters (PAEs), the pervasive and ubiquitous endocrine-disrupting chemicals of environmental concern, generated annually on a million-ton scale, are primarily employed as plasticisers in the production of a variety of plastic products and as additives in a large number of commercial supplies. The increased awareness of various adverse effects on the ecosystem and human health including reproductive and developmental disorders has led to a striking increase in research interest aimed at managing these man-made oestrogenic chemicals. In these circumstances, microbial metabolism appeared as the major realistic process to neutralise the toxic burdens of PAEs in an ecologically accepted manner. Among a wide variety of microbial species capable of degrading/transforming PAEs reported so far, bacteria-mediated degradation has been studied most extensively. The main purpose of this review is to provide current knowledge of metabolic imprints of microbial degradation/transformation of PAEs, a co-contaminant of plastic pollution. In addition, this communication illustrates the recent advancement of the structure-functional aspects of the key metabolic enzyme phthalate hydrolase, their inducible regulation of gene expression and evolutionary relatedness, besides prioritising future research needs to facilitate the development of new insights into the bioremediation of PAE in the environment.

Metabolic imprints in the hydrogen isotopes of Archaeoglobus fulgidus tetraether lipids

The stable hydrogen isotope composition of archaeal lipids is emerging as a potential paleoenvironmental proxy, adding to the well-established application of plant leaf wax-derived n-alkanes in paleohydrological reconstruction. A handful of studies reported relatively invariant and depleted hydrogen isotope compositions for archaeal lipids despite the range of different organisms and growth conditions explored. However, how modes of metabolism and physiological state (growth phase) affect the hydrogen isotope signatures of archaeal lipids remains poorly understood, limiting our ability to interpret archaeal lipid biomarker records from the environment. Here we conducted water isotope label experiments with a metabolically flexible and well-studied model archaeon Archaeoglobus fulgidus and quantified the hydrogen isotope fractionation between lipids and water in response to different carbon substrates and electron donor–acceptor pairs at different growth phases. The 2H/1H fractionation between lipids and water (εL/W) was overall negative. Both carbon metabolism and growth phase affected the magnitude of isotope fractionation in A. fulgidus; however, the changes in εL/W values were relatively subtle where they ranged from –283 to –229 ‰ across all tested conditions, overlapping with the ranges observed for other archaea in previous studies. Isotope flux-balance model results suggest that ≥ 80 % and ≥ 50 % of lipid-bound H in A. fulgidus cultures directly reflect water isotope compositions (i.e., not via organic substrate or H2) during autotrophy and heterotrophy, respectively. The model results also suggest two main mechanisms of consistent 2H depletion observed in A. fulgidus tetraethers as well as other archaeal lipids reported in previous studies: 1) isotopic re-equilibration via upstream isomerization reactions involving C5 units and 2) downstream double bond reduction catalyzed by a flavoenzyme geranylgeranyl reductase. These results are consistent with previous isotope flux-balance model results for a different archaeon. Finally, we synthesized available data to compare εL/W patterns across all three domains of life: Eukarya, Archaea and Bacteria. Because they vary fundamentally in lipid biosynthesis pathways, we present comparative discussions in pairs, focusing on the shared biochemical mechanisms among isoprenoid lipids and potential signals of metabolic adaptations across prokaryotic lipids. Emerging patterns between diverse archaeal and eukaryotic isoprenoid lipids are consistent with the two proposed mechanisms for 2H depletion identified (isomerization and final saturation). The patterns between archaeal isoprenoids and bacterial fatty acids suggest that the general state of energy limitation may also contribute to large, negative values of εL/W observed in prokaryotic lipids. Altogether, these findings lend further support for the potential of archaeal lipid εL/W as a paleohydrological proxy and provide a broader insight into the 2H/1H fractionation mechanisms potentially shared among prokaryotic and eukaryotic lipid biomarkers.

Hyperoxic recovery interferes with the metabolic imprint of hypoxic exercise

Supplemental oxygen (hyperoxia) improves physical performance during hypoxic exercise. Based on the analysis of metabolome and iron homeostasis from human athlete blood samples, we show that hyperoxia during recovery periods interferes with metabolic alterations following hypoxic exercise. This may impair beneficial adaptations to exercise and/or hypoxia and highlights risks of oxygen supplementation in hypoxia.

Metabolic imprinting in beef calves supplemented with creep feeding on performance, reproductive efficiency and metabolome profile

This experiment evaluated the influence of creep feeding supplementation on productive and reproductive performance and on serum metabolome profile in Nelore (Bos indicus) heifers. Female calves were assigned to treatments: Creep (n = 190), with ad libitum access to a nutritional supplement from 70 to 220 days after birth, or Control (n = 140), without supplementation. After weaning (Day 220), both groups followed the same pasture and nutritional management. Body weight (BW) and backfat thickness (BFAT) were measured over time. Blood samples were collected at 220 and 360 days for LC–MS/MS targeted metabolomics. On day 408, during the synchronization timed artificial insemination (TAI) protocol, reproductive status (RS: diameter of uterine horn and largest follicle, and presence of CL) was assessed. Creep feeding increased BW and BFAT at weaning, but no differences in BW, BFAT, or RS after weaning were observed. Nonetheless, the pregnancy per AI (P/AI) for 1st service was 28.9% higher in the Creep group. On day 220, 11 significant metabolites influenced five metabolic pathways: Glucose-alanine cycle, alanine, glutathione, phenylalanine and tyrosine metabolism, and urea cycle. On day 360, 14 significant metabolites influenced eight metabolic pathways: Malate-aspartate shuttle, arginine and proline metabolism, urea cycle, aspartate, beta-alanine, glutamate metabolism, ammonia recycling and citric acid cycle. In conclusion, creep feeding supplementation improved calf performance and induced metabolic changes at weaning and 360 days of age. Although heifers had similar productive performance and reproductive status, when submitted to TAI, those supplemented with creep feeding had greater P/AI.

Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. We investigated differences in serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at 6 months of age. We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum. Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of apolipoprotein E (apoE) ε4 carriers and replicating the serum metabolic imprint of the APOE ε4 genotype. Our work thus represents a significant step toward translating metabolic dysregulation from model organisms to human AD. This was a metabolomic assessment of two mouse models relevant to Alzheimer's disease. Mouse models exhibit broad sex-specific metabolic differences, similar to human study cohorts. The early-onset 5XFAD mouse model primarily alters brain metabolites while the late-onset LOAD1 model primarily changes serum metabolites. Apolipoprotein E (apoE) ε4 mice recapitulate glycerophospolipid signatures of human APOE ε4 carriers in both brain and serum.

Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.

24 Effects of Gestational and Postweaning Nutrition on Brain Development and Puberty in Beef Heifers

Abstract Approximately 5 million beef heifers enter the U.S. cow herd annually, and their lifetime productivity is largely dependent upon their ability to attain puberty and produce a calf by 24 mo of age. However, a considerable proportion of heifers within existing U.S. production systems fail to achieve these goals, particularly in southern regions where Bos indicus-influenced cattle predominate. Consequently, managerial approaches are needed that employ nutritional programming of the reproductive neuroendocrine axis, while minimizing feeding costs and optimizing the consistent attainment of puberty by approximately 14 mo of age. Our previous research has clearly demonstrated that increased BW gain between 4 and 8 mo of age facilitates pubertal development by programming hypothalamic centers that regulate gonadotropin releasing-hormone (GnRH) secretion. Among the different metabolic hormones, leptin has a critical role in conveying nutritional information to the hypothalamus and controlling puberty. Two hypothalamic neuronal populations that express the orexigenic peptide neuropeptide Y (NPY) and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH; a product of the POMC gene) are key components of afferent pathways that convey inhibitory (NPY) and excitatory (αMSH) inputs to GnRH and kisspeptin neurons. Our studies have demonstrated that short-term increases in dietary energy intake after early weaning at 4 mo of age result in epigenetic, structural, and functional modifications in these hypothalamic pathways to promote high-frequency, episodic release of GnRH and luteinizing hormone. However, integrating the foundational knowledge of metabolic imprinting of the brain for early puberty with issues related to lifetime performance is complex. One approach has been to employ a novel stair-step nutritional regimen involving alternating periods of dietary energy-restriction and re-feeding during juvenile development. This approach is designed to support early onset of puberty by imprinting functional alterations in the hypothalamus during key periods of brain development while optimizing other aspects of growth and performance. Finally, while several key processes of fetal brain development occur during late gestation, neither maternal undernutrition (BCS 3.0-3.5) nor maternal obesity (BCS 7.5-8.0) during the last two trimesters of gestation impacted the organization of hypothalamic neurocircuitries controlling GnRH/LH secretion or age at puberty in the heifer offspring. Collectively, these results indicate that the adult reproductive phenotype in Bos indicus-influenced females is resilient to significant degrees of nutritional stress imposed during prenatal development, particularly if early gestation (first trimester) is avoided. These findings are in contrast with reports in Bos taurus females in which late gestation nutritional extremes result in delayed puberty in heifer offspring, suggesting that potential genotype-specific differences may exist. Research support: USDA-NIFA-AFRI (2018-67015-27595 and 2021-67015-33676).

Multi-omic characterisation as a tool to improve knowledge, valorisation and conservation of wild fruit genetic resources: the case of Arbutus unedo L.

The valorisation and conservation of plant genetic resources (PGRs) and wild fruit PGRs are critical to ensure the maintenance of genetic and cultural heritage and to promote new perspectives on resource use. New strategies to characterize PGRs are needed, and the omics approach can provide information that is still largely unknown. The Strawberry tree (Arbutus unedo L.) is an underutilized, drought and fire-resistant species distributed in the Mediterranean area and its berries have large ethnobotanical use. Although their phenolic profile and antioxidant capacity are known, they are not well characterised, particularly from a proteomic perspective. The aim of this work is the characterisation of two ecotypes of A. unedo (Campania and Sicily) from a molecular viewpoint to valorise and encourage the preservation of this wild fruit. Samples were collected from two different geographical areas to assess whether different geographical conditions could influence the characteristics of leaves and fruits at the three stages of ripening (green, veraison, red). Proteomic analysis identified 904 proteins, of which 122 showed significance along the ripening. Some of these differentially abundant proteins, such as chalcone synthase, show a marked increase during ripening. The protein functional classes with the highest representation are involved in protein and amino acid metabolism, glycolysis and in secondary metabolism. From a proteomic perspective, there are no differences between the fruits from the two regions compared by the ripening stage. However, the pedoclimatic metabolic imprinting allowed the observation of good diversity in the metabolomic profiles between the two ecotypes, especially for anthocyanins, 4 times more abundant in the Sicilian veraisoned fruit than in the Campania one, and catechins, with double the abundance in the Campania ecotype compared to the Sicilian ecotype in the green phase, but more abundant (3x) in the Sicilian veraisoned fruit. Phenolic compounds show a 20% greater abundance in the Campania green arbutus fruit than in the Sicilian one, values that then equalise as ripening progresses. Multi-omic characterisation enhanced the knowledge on a wild fruit plant species which shows specific adaptations and responses to the environment to be considered when addressing the issue of local agrobiodiversity.

Metabolic imprint induced by seed halo-priming promotes a differential physiological performance in two contrasting quinoa ecotypes.

"Memory imprint" refers to the process when prior exposure to stress prepares the plant for subsequent stress episodes. Seed priming is a strategy to change the performance of seedlings to cope with stress; however, mechanisms associated with the metabolic response are fragmentary. Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Chenopodium quinoa Willd. (Amaranthaceae) is a promising crop to sustain food security and possesses a wide genetic diversity of salinity tolerance. To elucidate if the metabolic memory induced by seed halo-priming (HP) differs among contrasting saline tolerance plants, seeds of two ecotypes of Quinoa (Socaire from Atacama Salar, and BO78 from Chilean Coastal/lowlands) were treated with a saline solution and then germinated and grown under different saline conditions. The seed HP showed a more positive impact on the sensitive ecotype during germination and promoted changes in the metabolomic profile in both ecotypes, including a reduction in carbohydrates (starch) and organic acids (citric and succinic acid), and an increase in antioxidants (ascorbic acid and α-tocopherol) and related metabolites. These changes were linked to a further reduced level of oxidative markers (methionine sulfoxide and malondialdehyde), allowing improvements in the energy use in photosystem II under saline conditions in the salt-sensitive ecotype. In view of these results, we conclude that seed HP prompts a "metabolic imprint" related to ROS scavenger at the thylakoid level, improving further the physiological performance of the most sensitive ecotype.

ОТДЕЛЬНЫЕ АСПЕКТЫ ИМПРИНТИНГА В ФОРМИРОВАНИИ КОГНИТИВНЫХ НАРУШЕНИЙ У ДЕТЕЙ РАЗЛИЧНОГО ВОЗРАСТА

Understanding of the processes that underlie brain development is of great clinical importance because it helps determining endo- and exogenous factors that may influence the neurocognitive abilities of human progeny. It is known that cognitive functions of children largely depend on the prenatal and intrauterine environment, which denotes that programming of future health occurs even before the birth of a fetus. This bibliographical review considers some environmental factors, such as neurohormonal, alimentary, and somatic, that influence the formation of the concept of metabolic imprinting, which in its turn allows determining the main risk groups and directions for therapeutic and preventive measures with the purpose of formation of mother's health for future healthy progeny, including the cognitive functions. The following databases were studied thoroughly in this review: PubMed®, Wiley Online Library, and eLIBRARY; the sources dated 2000 to 2021 were used.

Adverse perinatal conditions and the developmental origins of thyroid dysfunction-Lessons from Animal Models.

Nutritional, hormonal, and environmental status during development can predispose the individual to obesity and endocrine diseases later in life, an association known as metabolic programming. In general, weight loss or gain are seen in thyroid disorders, and thyroid function can be affected by body adiposity. In addition, hyper- and hypothyroidism can be related to metabolic programming. Our aim was to gather evidence that regardless of the type or critical window of metabolic imprinting, offspring exposed to certain adverse perinatal conditions have a higher risk of developing thyroid dysfunction. We reviewed literature data that relate insults occurring during pregnancy and/or lactation to short- and long-term offspring thyroid dysfunction in animal models. Few studies have addressed the hypothalamic-pituitary-thyroid axis and thyroid dysfunction related to metabolic programming. The literature shows that under- and overnutrition, exposure to endocrine disruptors, early weaning, maternal thyroid disease and maternal high-fat diet can induce alterations in offspring thyroid function in a sex-dependent manner. Based on the few available data, mainly in rodent models, we can conclude that diet, hormones, and environmental contaminants are related to the developmental origins of later thyroid dysfunction by interrupting the normal maturation of the thyroid gland.

Metabolic imprinting induced by a high-sugar diet: effects on microRNA expression and insulin resistance in young rats.

Metabolic imprinting describes associations between nutritional experiences of early life and the development of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet (HSD) and its effects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the effects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. Weaned male Wistar rats (N = 6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-, or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometabolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N = 3). The HSD resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent effect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with the improvement in IR observed after a 12-week HSD feeding period. This is the first time that excessive sugar intake post-weaning has been associated with miRNA production by rWAT with an impact on IR development.

Inhibition of IRAK4 dysregulates SARS-CoV-2 spike protein-induced macrophage inflammatory and glycolytic reprogramming.

Escalated innate immunity plays a critical role in SARS-CoV-2 pathology; however, the molecular mechanism is incompletely understood. Thus, we aim to characterize the molecular mechanism by which SARS-CoV-2 Spike protein advances human macrophage (Mϴ) inflammatory and glycolytic phenotypes and uncover novel therapeutic strategies. We found that human Mϴs exposed to Spike protein activate IRAK4 phosphorylation. Blockade of IRAK4 in Spike protein-stimulated Mϴs nullifies signaling of IRAK4, AKT, and baseline p38 without affecting ERK and NF-κB activation. Intriguingly, IRAK4 inhibitor (IRAK4i) rescues the SARS-CoV-2-induced cytotoxic effect in ACE2+HEK 293 cells. Moreover, the inflammatory reprogramming of Mϴs by Spike protein was blunted by IRAK4i through IRF5 and IRF7, along with the reduction of monokines, IL-6, IL-8, TNFα, and CCL2. Notably, in Spike protein-stimulated Mϴs, suppression of the inflammatory markers by IRAK4i was coupled with the rebalancing of oxidative phosphorylation over metabolic activity. This metabolic adaptation promoted by IRAK4i in Spike protein-activated Mϴs was shown to be in part through constraining PFKBF3, HIF1α, cMYC, LDHA, lactate expression, and reversal of citrate and succinate buildup. IRAK4 knockdown could comparably impair Spike protein-enhanced inflammatory and metabolic imprints in human Mϴs as those treated with ACE2, TLR2, and TLR7 siRNA. Extending these results, in murine models, where human SARS-CoV-2 Spike protein was not recognized by mouse ACE2, TLRs were responsible for the inflammatory and glycolytic responses instigated by Spike protein and were dysregulated by IRAK4i therapy. In conclusion, IRAK4i may be a promising strategy for severe COVID-19 patients by counter-regulating ACE2 and TLR-mediated Mϴ hyperactivation.Graphical abstract IRAK4i therapy counteracts Mϴ inflammatory and glycolytic reprogramming triggered by Spike protein. This study illustrates that SARS-CoV-2 Spike protein activates IRAK4 signaling via ACE2 as well as TLR2 and TLR7 sensing in human Mϴs. Remarkably, IRAK4i treatment can dysregulate both ACE-dependent and independent (via TLR sensing) SARS-CoV-2 Spike protein-activated inflammatory and metabolic imprints.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00018-022-04329-8.

COVID‐19‐specific metabolic imprint yields insights into multiorgan system perturbations

Corona disease 2019 (COVID‐19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID‐19 severity. However, several questions pertain with respect to the metabolome in COVID‐19. We performed an in‐depth assessment of 1129 unique metabolites in 27 hospitalized COVID‐19 patients and integrated results with large‐scale proteomic and immunology data to capture multiorgan system perturbations. More than half of the detected metabolic alterations in COVID‐19 were driven by patient‐specific confounding factors ranging from comorbidities to xenobiotic substances. Systematically adjusting for this, a COVID‐19‐specific metabolic imprint was defined which, over time, underwent a switch in response to severe acute respiratory syndrome coronavirus‐2 seroconversion. Integration of the COVID‐19 metabolome with clinical, cellular, molecular, and immunological severity scales further revealed a network of metabolic trajectories aligned with multiple pathways for immune activation, and organ damage including neurological inflammation and damage. Altogether, this resource refines our understanding of the multiorgan system perturbations in severe COVID‐19 patients.

Dietary curcumin supplementation promotes browning and energy expenditure in postnatal overfed rats

BackgroundEarly postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and resultsThis study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.ConclusionDietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.

Impacts of Nutritional Management During Early Postnatal Life on Long-Term Physiological and Productive Responses of Beef Cattle

Effective early postnatal nutritional management is a crucial component of livestock production systems, and nutrient manipulation during this period has been shown to exert long-term consequences on beef cattle growth and physiology. Metabolic imprinting defines these biological responses to a nutritional intervention early in life that permanently alter physiological outcomes later in life. Early weaning has been used to study metabolic imprinting effects, given that it allows for nutritional manipulation of animals at a young age. This practice has been shown to enhance carcass characteristics in feedlot cattle and accelerate reproductive development of females. Another strategy to study the effects of metabolic imprinting without the need for early weaning is to provide supplements via creep feeding. Providing creep feed to nursing cattle has resulted in transient and long-term alterations in cattle metabolism, contributing to increased reproductive performance of developing heifers and enhanced carcass quality of feeder cattle. Collectively, results described herein demonstrate nutrient manipulation during early postnatal life exerts long-term consequences on beef cattle productivity and may be a strategy to optimize production efficiency in beef cattle systems.

A Clinical Trial for the Identification of Metabolic Biomarkers in Hashimoto's Thyroiditis and in Psoriasis: Study Protocol.

Hashimoto’s thyroiditis and psoriasis are inflammatory disorders that significantly impact patients’ quality of life, stressing the need for novel biomarkers of early diagnosis. This randomized clinical trial (NCT04693936) aims to identify Hashimoto’s thyroiditis’ and psoriasis’ metabolic biomarkers and to investigate the effect of environmental factors on the disease-related metabolic imprint and quality of life. Patients with Hashimoto’s thyroiditis, patients with psoriasis, and healthy individuals aged 18–60 will be recruited, enrolled according to eligibility criteria (medical history, clinical thyroid markers and the PASI score) and randomized to two groups. The intervention group will receive a combination of nutraceuticals for 6 months as part of a Mediterranean diet, and the control group will follow their usual diet. Data will be collected at baseline and the end of the study, including metabolite levels, lifestyle and anthropometric measurements, adherence to the Mediterranean diet (through the Mediterranean Diet Score) and disease-specific quality of life (through the Thyroid Patient Report Outcome for Hashimoto’s group, and the Dermatology Life Quality Index for the psoriasis group). This study will investigate metabolic biomarkers and related changes in Hashimoto’s thyroiditis and psoriasis and evaluate the association of metabolic changes with dietary factors and quality of life.

Effects of early high nutrition related to metabolic imprinting events on growth, carcass characteristics, and meat quality of grass-fed Wagyu (Japanese Black cattle).

The study was conducted to clarify how early high plane of nutrition related to metabolic imprinting affected growth, carcass characteristics, and meat quality of grass-fed Wagyu (Japanese Black cattle). Wagyu steers were allocated randomly into 2 dietary groups: (1) steers fed milk replacer (crude protein 26.0%, crude fat 25.5%; maximum intake 0.6 kg/d) until 3 mo of age and then fed roughage (orchard grass hay) ad libitum from 4 to 10 mo of age (roughage group, RG; n = 11); (2) steers fed milk replacer (maximum intake of 1.8 kg/d) until 3 mo of age and then fed a high-concentrate diet from 4 to 10 mo of age (early high nutrition, EHN; n = 12). After 11 mo of age, all steers were fed roughage ad libitum until 31 mo of age and then slaughtered. Growth performance, carcass traits, longissimus muscle (LM) meat quality and intramuscular fat (IMF) content, plasma insulin-like growth factor I (IGF-I) concentration, and bone mineral density were measured. Body weight was greater in EHN steers (571 kg) than RG steers (520 kg; P < 0.01). Plasma IGF-I levels were higher in EHN steers than in RG steers at 3, 10, and 14 mo of age (P < 0.01, P < 0.005, P < 0.001, respectively); however, plasma IGF-I levels were lower in EHN steers compared with RG steers at 30 mo of age (P < 0.01). The total weight of the muscles and bones of the left half of the carcass was not different between the 2 groups (P = 0.065). Five of the 19 muscles investigated (semimembranosus, P = 0.036; infraspinatus, P = 0.024; supraspinatus, P = 0.0019; serratus ventralis cervicis, P = 0.032; serratus ventralis thoracis, P = 0.027) were heavier in EHN steers. Total fat weight in the left half of the carcass was 30% greater (P = 0.025) in HNE carcasses. Subcutaneous and perirenal fat weights were 53% and 84% greater (P = 0.008, P = 0.002, respectively) in EHN carcasses. The LM IMF content was greater in EHN loins (13.2%) compared with RG loins (9.4%) at 31 mo of age (P = 0.038); however, no differences were found for shear force, tenderness, and cook loss. These results suggested early high-nutrition affected the growth and meat quality of livestock.

Disarranged neuroplastin environment upon aging and chronic stress recovery in female Sprague Dawley rats.

Chronic stress produces long‐term metabolic changes throughout the superfamily of nuclear receptors, potentially causing various pathologies. Sex hormones modulate the stress response and generate a sex‐specific age‐dependent metabolic imprint, especially distinct in the reproductive senescence of females. We monitored chronic stress recovery in two age groups of female Sprague Dawley rats to determine whether stress and/or aging structurally changed the glycolipid microenvironment, a milieu playing an important role in cognitive functions. Old females experienced memory impairment even at basal conditions, which was additionally amplified by stress. On the other hand, the memory of young females was not disrupted. Stress recovery was followed by a microglial decrease and an increase in astrocyte count in the hippocampal immune system. Since dysfunction of the brain immune system could contribute to disturbed synaptogenesis, we analyzed neuroplastin expression and the lipid environment. Neuroplastin microenvironments were explored by analyzing immunofluorescent stainings using a newly developed Python script method. Stress reorganized glycolipid microenvironment in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) hippocampal regions of old females but in a very different fashion, thus affecting neuroplasticity. The postulation of four possible neuroplastin environments pointed to the GD1a ganglioside enrichment during reproductive senescence of stressed females, as well as its high dispersion in both regions and to GD1a and GM1 loss in the CA1 region. A specific lipid environment might influence neuroplastin functionality and underlie synaptic dysfunction triggered by a combination of aging and chronic stress.

Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease.

Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.