EJE Prize 2023: genes on steroids-genomic control of hepatic metabolism by the glucocorticoid receptor.

Glucocorticoids are essential hormones produced by the adrenal cortex with prominent circadian rhythmicity and in times of stress. Glucocorticoids maintain liver homeostasis through coordinated activities that control the major pathways of energy metabolism. Glucocorticoids activate the glucocorticoid receptor (GR), a nuclear hormone receptor that regulates the transcription of hundreds of genes in response to ligand.

Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.

Objectives: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.

Skin Autofluorescence Mirrors Surrogate Parameters of Vascular Aging: An Enable Study.

Advanced glycation end-products (AGEs) are implicated in vascular aging due to their pro-inflammatory properties. Skin autofluorescence (SAF) is a measure to estimate their deposition. It is an easily quantifiable marker that has been shown to correlate with cardiovascular risk and parameters of metabolic diseases.

Specific miRNAs are associated with human cancer cachexia in an organ-specific manner.

Background: Cancer cachexia (CCx) is a complex and multi-organ wasting syndrome characterized by substantial weight loss and poor prognosis. An improved understanding of the mechanisms involved in the onset and progression of cancer cachexia is essential. How microRNAs contribute to the clinical manifestation and progression of CCx remains elusive.

promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature.

Objective: infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between infection and colon cancer is lacking.

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease.

Background: Crohn's disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation.

Results: We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including Tnf and SAMP/Yit mice.

Amount and composition of total fatty acids in red and yellow bone marrow are altered with changes in bone mineral density.

There is general consent that with decreasing bone mineral density the amount of marrow adipose tissue increases. While image-based techniques, claim an increase in saturated fatty acids responsible for this effect, this study shows an increase in both saturated and unsaturated fatty acids in the bone marrow. Using fatty acid methyl ester gas chromatography-mass spectrometry, characteristic fatty acid patterns for patients with normal BMD (N = 9), osteopenia (N = 12), and osteoporosis (N = 9) have been identified, which differ between plasma, red bone marrow and yellow bone marrow.

Thermogenic Capacity of Human Supraclavicular Brown Fat and Cold-Stimulated Brain Glucose Metabolism.

Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of , which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress.

Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life.

The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions.

Effects of Dairy Intake on Markers of Cardiometabolic Health in Adults: A Systematic Review with Network Meta-Analysis.

The health effects of dairy products are still a matter of scientific debate owing to inconsistent findings across trials. Therefore, this systematic review and network meta-analysis (NMA) aimed to compare the effects of different dairy products on markers of cardiometabolic health. A systematic search was conducted in 3 electronic databases [MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science; search date: 23 September 2022].

Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290).

Sweetener System Intervention Shifted Neutrophils from Homeostasis to Priming.

Background: Non-nutritive sweeteners (NNS) are part of personalized nutrition strategies supporting healthy glycemic control. In contrast, the consumption of non-nutritive sweeteners has been related to person-specific and microbiome-dependent glycemic impairments. Reports on the effects of NNS on our highly individual cellular immune system are sparse.

Machine learning reveals STAT motifs as predictors for GR-mediated gene repression.

Glucocorticoids are potent immunosuppressive drugs, but long-term treatment leads to severe side-effects. While there is a commonly accepted model for GR-mediated gene activation, the mechanism behind repression remains elusive. Understanding the molecular action of the glucocorticoid receptor (GR) mediated gene repression is the first step towards developing novel therapies.

Draft Genome Sequence of a Preterm Infant-Derived Isolate of Candida parapsilosis.

Candida parapsilosis is a human fungal pathogen of increasing incidence and causes invasive candidiasis, notably in preterm or low-birthweight neonates. Here, we present the genome sequence of C. parapsilosis NCYC 4289, a fecal isolate from a preterm male infant.

Secretin modulates appetite via brown adipose tissue-brain axis.

Purpose: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown.

Methods And Results: In this placebo-controlled, single-blinded neuroimaging study, firstly using [F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis.

Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets.

Bifidobacterium bacteraemia is rare with routine probiotics use in preterm infants: A further case report with literature review.

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago.

Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value).

This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value.

Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis.

Background & Aims: Hepatocyte growth and proliferation depends on membrane phospholipid biosynthesis. Short-chain fatty acids (SCFAs) generated by bacterial fermentation, delivered through the gut-liver axis, significantly contribute to lipid biosynthesis. We therefore hypothesized that dysbiotic insults like antibiotic treatment not only affect gut microbiota, but also impair hepatic lipid synthesis and liver regeneration.

The Development of the Bacterial Community of Brown Trout () during Ontogeny.

Brown trout () is an important aquaculture species in Germany, but its production faces challenges due to global warming and a high embryo mortality. Climate factors might influence the fish's bacterial community (BC) and thus increase embryo mortality. Yet, knowledge of the physiological BC during ontogeny in general is scarce.

When should I eat: A circadian view on food intake and metabolic regulation.

The circadian clock is a hierarchical timing system regulating most physiological and behavioral functions with a period of approximately 24 h in humans and other mammalian species. The circadian clock drives daily eating rhythms that, in turn, reinforce the circadian clock network itself to anticipate and orchestrate metabolic responses to food intake. Eating is tightly interconnected with the circadian clock and recent evidence shows that the timing of meals is crucial for the control of appetite and metabolic regulation.