Daily Profile of miRNAs in the Rat Colon and In Silico Analysis of Their Possible Relationship to Colorectal Cancer.

Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues.

Adipocyte-specific deletion of gp130 prevents ketogenic diet-induced hepatic steatosis.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of obesity and type 2 diabetes, can progress to metabolic dysfunction-associated steatohepatitis and fibrosis. MASLD is characterized by elevated hepatic lipid accumulation (steatosis) and insulin resistance. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, induces hepatic insulin resistance and steatosis in animal models through unknown mechanisms.

NRAC controls CD36-mediated fatty acid uptake in adipocytes and lipid clearance in vivo.

Adipose tissue is a central organiser of systemic lipid homeostasis and a pharmacological target in obesity, orchestrating cellular responses to environmental cues. Nutritionally regulated adipose and cardiac enriched protein (NRAC) is a small adipocyte-specific transmembrane protein with unknown function. Here, we show that Nrac directly interacts with scavenger receptor CD36 via its first transmembrane domain.

HOOK1 gene expression and DNA methylation in obesity and related cardiometabolic traits.

Background: Accumulation of fat in omental visceral adipose tissue is strongly linked to metabolic diseases. Our recent findings show a distinct and more accessible chromatin landscape of the visceral depot compared to its subcutaneous counterpart. Based on integrated analysis of chromatin accessibility and transcriptomics, we identified previously unrecognized genes linked with obesity.

Enhanced Media Optimize Bovine Myogenesis in 2D and 3D Models for Cultivated Meat Applications.

Livestock farming and conventional meat production pose significant environmental, health, and animal welfare challenges. In seeking sustainable alternative solutions, cultivated meat technology typically utilizes differentiation of myogenic progenitor cells (MPCs) into muscle cells for in vitro meat production. However, understanding the molecular determinants governing MPC differentiation into muscle cells, and the potential enhancement of this process through modulation of signaling pathways, remains limited.

B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity.

Immune-derived opioid peptides have been implicated in immune regulation and inflammatory processes. Here, we investigate the effects of nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in obesity. Selectively targeting N/OFQ, encoded by the gene, in B cells mitigates the adverse metabolic effects of diet-induced obesity and enhances insulin sensitivity and glucose tolerance.

An epigenome atlas of mouse adipocytes.

Objective: Epigenetic modifications including histone post translational modifications can influence gene expression in adipocytes, potentially contributing to metabolic dysfunctions, obesity, and insulin resistance. Despite recent advances in the characterization of the mouse adipocyte epigenome, epigenetic characterization of adipocytes in vivo has been challenging, particularly across different adipose depots and of several epigenetic modifications.

Methods: Here, we use specific reporter mice labelling brown, beige and white adipocytes, diphtheria toxin-mediated ablation of beige adipocytes, and Cleavage Under Targets and Tagmentation (CUT&Tag) to generate paired single mouse datasets of five histone marks.

Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted.

: Immune-related cutaneous adverse events (ircAEs) are common complications of cancer immunotherapy and provide insight into immune-related adverse events (irAEs) more broadly. To enhance our molecular understanding, we characterized ircAEs resulting from single-agent (PD1) and combined immunotherapy regimens (P+C). Clinically, maculopapular rash (MPR) and toxic epidermal necrolysis (TEN) resemble ircAEs, providing a valuable basis for investigations.

Glucagon controls obesity-specific energy expenditure via persistent cAMP/PKA signaling.

Background & Aims: Glucagon (GCG) analogues are gaining attention as promising components in incretin-based therapeutics for obesity and metabolic dysfunction-associated steatohepatitis. However, the biological effects of chronic GCG treatment, particularly the molecular underpinnings of GCG-induced energy expenditure and lipid metabolism, remain poorly defined.

Methods: We utilized a long-acting GCG analogue (LA-GCG) in conjunction with hepatic and adipose glucagon receptor (GCGR) knockout mouse models.

Sarcospan, a candidate gene of fat distribution, may affect lipid storage in adipocytes.

Background And Aims: Genetic and epigenetic variations in the Sarcospan (SSPN) gene are associated with parameters of fat distribution (body mass index, waist-to-hip ratio), glucose homeostasis and adipocyte size in human potentially by affecting adipogenesis. This study aims at clarifying the impact of SSPN on adipogenesis, particularly focusing on its promoter methylation.

Materials And Methods: Immortalized murine epididymal preadipocytes were transfected with fluorescence-marked plasmids coding for DNMT3a, CRISPR/dCas9-Suntag and vectors carrying guide RNAs complementary to the transcription start site region and differentiated to mature adipocytes.

Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution.

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis.

Abundance of a metabolically active subpopulation in dedifferentiated adipocytes inversely correlates with body mass index.

Objective: The cellular composition and functionality of adipose tissue are key determinants of metabolic diseases associated with adipose tissue dysregulation, such as obesity. We hypothesized that distinct subpopulations with unique gene expression profiles and functional characteristics exist within human adipocytes.

Methods: Dedifferentiated adipocytes (DFAT), obtained by ceiling culture of human adipocytes, were analyzed using single-cell RNA sequencing (10x Genomics).

Tebentafusp elicits on-target cutaneous immune responses driven by cytotoxic T cells in uveal melanoma patients.

BACKGROUNDTebentafusp is the first T cell receptor-based bispecific protein approved for clinical use in HLA-A*02:01+ adult patients with unresectable/metastatic uveal melanoma. It redirects T cells toward gp100-expressing target cells, frequently inducing skin-related early adverse events.METHODSThis study investigated immunological and cellular responses using single-cell and spatial analysis of skin biopsies from patients with metastatic uveal melanoma treated with tebentafusp.

Association of Lifestyle-Induced Weight Loss With Gene Expression in Subcutaneous Adipose Tissue in Metabolic Syndrome.

Aims: Lifestyle-induced weight loss (LIWL) is considered an effective therapy for the treatment of metabolic syndrome (MetS). The role of differentially expressed genes (DEGs) in adipose tissue function and in the success of LIWL in MetS is still unclear. We investigated the effect of 6 months of LIWL on transcriptional regulation in subcutaneous adipose tissue (SAT).

The serine protease KLK7 promotes immune cell infiltration in visceral adipose tissue in obesity.

Obesity is a major health problem associated with global metabolic dysfunction and increased inflammation. It is thus critical to identify the mechanisms underlying the crosstalk between immune cells and adipose tissue that drive cardiovascular and metabolic dysfunction in obesity. Expression of the kallikrein-related serine protease 7 (KLK7) in adipose tissue is linked to inflammation and insulin resistance in high fat diet (HFD)-fed mice.

Chromatin landscape in paired human visceral and subcutaneous adipose tissue and its impact on clinical variables in obesity.

Background: Obesity is a global health challenge and adipose tissue exhibits distinct depot-specific characteristics impacting differentially on the risk of metabolic comorbidities.

Methods: Here, we integrate chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data from intra-individually paired human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples to unveil depot-specific regulatory mechanisms.

Findings: We identified twice as many depot-specific differentially accessible regions (DARs) in OVAT compared to SAT.

Glutamatergic argonaute2 promotes the formation of the neurovascular unit in mice.

Proper formation of the complex neurovascular unit (NVU) along with the blood-brain barrier is critical for building and sustaining a healthy, functioning central nervous system. The RNA binding protein argonaute2 (Ago2) mediates microRNA (miRNA)-mediated gene silencing, which is critical for many facets of brain development, including NVU development. Here, we found that in glutamatergic neurons was critical for NVU formation in the developing cortices of mice.

adiposetissue.org: A knowledge portal integrating clinical and experimental data from human adipose tissue.

We developed the Adipose Tissue Knowledge Portal by centralizing previously dispersed datasets, integrating clinical and experimental results with transcriptomic and proteomic data from >6,000 women and men. The platform includes multiple adipose depots, resident cell types, and adipocyte perturbation studies. By providing streamlined data access, the portal enables integrative analyses and serves as a powerful tool to interrogate various dimensions of adipose biology down to the single-cell level.

Sex-specific role of epigenetic modification of a leptin upstream enhancer in adipose tissue.

Objective: Maternal hormonal status can have long-term effects on offspring metabolic health and is likely regulated via epigenetic mechanisms. We elucidated the effects of maternal thyroid hormones on the epigenetic regulation of leptin (Lep) transcription in adipose tissue (AT) and subsequently investigated the role of DNA methylation at a Lep upstream enhancer (UE) in adipocyte biology.

Results: Pregnant mice treated with triiodothyronine (T3) produced offspring with reduced body weight, total fat mass, and gonadal white adipose tissue (gWAT) mass at 6 months of age (treatment: N = 8; control: N = 12).

Short-term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: Glucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms.

Research Design And Methods: This single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants.

Unveiling adipose populations linked to metabolic health in obesity.

Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity.

Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation.

The significance of thyroid hormones (THs) in beige adipocyte thermogenesis remains incompletely understood. We previously reported that THs directly regulate the expression of zinc-finger protein 423 (ZFP423), an anti-thermogenic factor, in adipose tissue. This study investigates the interaction between THs and adrenergic signaling in regulating thermogenic capacity and activation of beige adipocytes formed in response to Zfp423 deletion.

Adipose tissue retains an epigenetic memory of obesity after weight loss.

Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown.

Expression of Intelectin-1, also known as Omentin-1, is related to clinical phenotypes such as overweight, obesity, insulin resistance, and changes after bariatric surgery.

Intelectin-1 (ITLN1; also Omentin-1, OMNT1) is secreted by adipose tissue (AT) and plays an important role in glucose metabolism regulation, with links to obesity-associated diseases. ITLN1 activity so far has rarely been investigated using RNA-sequencing and in larger cohorts. We evaluated ITLN1 expression among three clinical cohorts of the Leipzig Obesity BioBank-a cross-sectional cohort comprising of 1480 people, a cohort of people with metabolically healthy or unhealthy obesity (31 insulin-sensitive, 42 insulin-resistant individuals with obesity), and a longitudinal two-step bariatric surgery cohort (n = 65).