The effect of Mankai plant consumption on postprandial glycaemic response among patients with type 2 diabetes: A randomized crossover trial.

Aim: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D).

Methods: In a 4-week, randomized crossover-controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%-8.

sNucConv: A bulk RNA-seq deconvolution method trained on single-nucleus RNA-seq data to estimate cell-type composition of human adipose tissues.

Deconvolution algorithms mostly rely on single-cell RNA-sequencing (scRNA-seq) data applied onto bulk RNA-sequencing (bulk RNA-seq) to estimate tissues' cell-type composition, with performance accuracy validated on deposited databases. Adipose tissues' cellular composition is highly variable, and adipocytes can only be captured by single-nucleus RNA-sequencing (snRNA-seq). Here we report the development of sNucConv, a Scaden deep-learning-based deconvolution tool, trained using 5 hSAT and 7 hVAT snRNA-seq-based data corrected by (i) snRNA-seq/bulk RNA-seq highly correlated genes and (ii) individual cell-type regression models.

Editor's Choice - Ten Year Time Trends of Amputation Surgery in Peripheral Arterial Disease in Germany: Before and During the COVID-19 Pandemic.

Objective: Peripheral arterial disease (PAD) has been associated with suboptimal treatment, high mortality, and high amputation rates. It is unclear how the COVID-19 (coronavirus disease 2019) pandemic affected this development in a long term context.

Methods: This is a registry based, retrospective, nationwide cohort study including patients hospitalised with PAD as a main or secondary diagnosis and amputation surgery between 2012 - 2021 in Germany.

CD4CD8α T Cell Clonal Expansion Dependent on Costimulation in Patients With Rheumatoid Arthritis.

Objective: CD4CD8 T cells are increased in patients with rheumatoid arthritis (RA). They are not only associated with joint erosions in established disease but are also present in the preclinical stages of RA. This study aims to further investigate their expansion in the context of T cell clonality in patients with RA, as well as their responsiveness to T cell-targeted treatment.

Dysregulated cytokine and oxidative response in hyper-glycolytic monocytes in obesity.

Introduction: Obesity is associated with a plethora of health complications, including increased susceptibility to infections or decreased vaccine efficacy, partly due to dysregulated immune responses. Monocytes play a crucial role in innate immunity, yet their functional alterations in obesity remain poorly understood.

Methods: Here, we employed proteomic and metabolomic analyses to investigate monocyte characteristics in individuals with overweight, obesity, impaired glucose tolerance (IGT), and type 2 diabetes (T2D), compared to lean donors.

Fas (CD95) expression in adipocytes contributes to diet-induced obesity.

Objective: Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.

Methods: Adipocyte-specific Fas knockout (Fas) and control littermate (Fas) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks.

Visceral fat mass dynamics in a 2-year randomized STrength versus ENdurance training trial in people with obesity.

Aim: To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity.

Materials And Methods: For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint.

Novel Long Noncoding RNA Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing.

Background: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood.

Methods: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called (heart failure-associated transcript 4).

Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgery.

Background: Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood.

Methods: Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N = 6 female) with severe obesity pre- and post-surgery.

Diurnal rythm of Nampt is gender and weight dependent.

Research Aim: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight.

GABAergic disinhibition from the BNST to PNOC neurons promotes HFD-induced hyperphagia.

Activation of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus (ARC) promotes high-fat-diet (HFD)-induced hyperphagia. In turn, PNOC neurons can inhibit the anorexic response of proopiomelanocortin (POMC) neurons. Here, we validate the necessity of PNOC activity for HFD-induced inhibition of POMC neurons in mice and find that PNOC-neuron-dependent inhibition of POMC neurons is mediated by gamma-aminobutyric acid (GABA) release.

Unveiling the dynamics of acetylation and phosphorylation in SGBS and 3T3-L1 adipogenesis.

Obesity, characterized by enlarged and dysfunctional adipose tissue, is among today's most pressing global public health challenges with continuously increasing prevalence. Despite the importance of post-translational protein modifications (PTMs) in cellular signaling, knowledge of their impact on adipogenesis remains limited. Here, we studied the temporal dynamics of transcriptome, proteome, central carbon metabolites, and the acetyl- and phosphoproteome during adipogenesis using LC-MS/MS combined with PTM enrichment strategies on human (SGBS) and mouse (3T3-L1) adipocyte models.

Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs), which influences offspring development and adult phenotypes. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health.

Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: the DIRECT-PLUS trial.

Objective: The objective of this study was to explore the effects of a green Mediterranean (green-MED) diet, which is high in dietary polyphenols and green plant-based protein and low in red/processed meat, on cardiovascular disease and inflammation-related circulating proteins and their associations with cardiometabolic risk parameters.

Methods: In the 18-month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green-MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green-MED diet group also consumed green tea (3-4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat.

Randomized Trial Comparing a Stent-Avoiding With a Stent-Preferred Strategy in Complex Femoropopliteal Lesions.

Background: Limited comparative data exist on different interventional strategies for endovascular revascularization of complex femoropopliteal interventions.

Objectives: In this study, the authors aimed to compare a stent-avoiding (SA) vs a stent-preferred (SP) strategy, promoting optimal lesion preparation and the use of drug-eluting technologies in both arms.

Methods: Within a prospective, multicenter, pilot study, 120 patients with symptomatic complex femoropopliteal lesions (Rutherford classification 2-4, mean lesion length 187.

Patients' perspective on their drug therapy after bariatric surgery: A quantitative, cross-sectional interview study.

Drug therapy in patients who have undergone bariatric surgery is challenging. We aimed to investigate the patients' perspective on their drug therapy. This should allow deriving tailored measures to better support patients and their healthcare professionals with drug therapy after bariatric surgery.

ELECT: prospective, randomized trial comparing microvascular plug versus platinum-fibered microcoils for embolization of aneurysm sac side branches before endovascular aortic aneurysm repair.

Background: Preemptive selective embolization of aneurysm sac side branches (ASSBs) has been proposed to prevent type II endoleak after endovascular aortic aneurysm repair (EVAR). This study aimed to explore if an embolization strategy using microvascular plugs (MVP) reduces intervention time and radiation dose compared to platinum-fibered microcoils. Furthermore, the effectiveness of the devices in occluding the treated artery was assessed.

Endovascular occlusion of segmental arteries feeding the anterior spinal artery to stage endovascular thoracoabdominal aortic repair.

Objective: Minimally invasive segmental artery coil embolization was introduced to prevent spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms. There is no consensus on whether the endovascular occlusion of segmental arteries feeding directly the anterior radiculomedullary artery and anterior spinal artery can be safely performed without causing spinal cord ischemia. Our aim was to investigate the feasibility and clinical impact of endovascular occlusion of segmental arteries supplying the anterior spinal artery during minimally invasive segmental artery coil embolization in patients with thoracoabdominal aortic aneurysms.

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity.

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance.

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus.

The increased risk of fractures in patients with type 1 diabetes mellitus (T1DM) is nowadays well recognized. However, the exact mechanism of action of diabetic bone disease has not been fully elucidated. MicroRNAs (miRNAs) are gene regulators that operate post-transcriptionally and have been implicated in the development of various metabolic disorders including T1DM.

EMC10 modulates hepatic ER stress and steatosis in an isoform-specific manner.

Background & Aims: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis.

Metabolomics in human SGBS cells as new approach method for studying adipogenic effects: Analysis of the effects of DINCH and MINCH on central carbon metabolism.

Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the use of phthalates, there has been a shift to safer declared substitutes, including the plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). Notwithstanding, recent studies suggest that the primary metabolite monoisononyl-cyclohexane-1,2-dicarboxylic acid ester (MINCH), induces differentiation of human adipocytes and affects enzyme levels of key metabolic pathways.

Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes: The DIRECT PLUS clinical trial.

Background And Aims: We demonstrated in the randomized 18-month DIRECT PLUS trial (n = 294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with 2 other healthy diets, reducing NAFLD by half, regardless of similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention.

Approach And Results: We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%).

High-resolution genomic profiling and locus-specific FISH in subcutaneous and visceral adipose tissue of obese patients.

Obesity is known as a heterogeneous and multifactorial disease. The distribution of body fat is crucial for the development of metabolic complications. Comprehensive genetic analyses on different fat tissues are rare but necessary to provide more detailed information.

Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength.

Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders.