Suboptimal dietary patterns are associated with accelerated biological aging in young adulthood: A study with twins.

Background & Aims: Suboptimal diets increase morbidity and mortality risk. Epigenetic clocks are algorithms that can assess health and lifespan, even at a young age, before clinical manifestations of diseases. We investigated the association between dietary patterns and biological aging in young adult twins.

Integration of single cell omics with biobank data discovers effects of abdominal obesity risk variants on adipocyte expression of more than 100 genes.

Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral adipose tissue (VAT), in their depot-specific contributions to cardiometabolic health. We integrated cell-type level RNA- and ATAC-seq data from human SAT and VAT biopsies and cell-lines to comprehensively elucidate transcriptomic, epigenetic, and genetic differences between the two fat depots. We identify cell-type marker genes for tissue specificity and functional enrichment, and show through genome-wide association study (GWAS) and partitioned polygenic risk score (PRS) enrichment analyses that the marker genes upregulated in SAT adipocytes have more prominent roles in abdominal obesity than those of VAT.

Single-cell DNA methylome and 3D genome atlas of the human subcutaneous adipose tissue.

Human subcutaneous adipose tissue (SAT) contains a diverse array of cell-types; however, the epigenomic landscape among the SAT cell-types has remained elusive. Our integrative analysis of single-cell resolution DNA methylation and chromatin conformation profiles (snm3C-seq), coupled with matching RNA expression (snRNA-seq), systematically cataloged the epigenomic, 3D topology, and transcriptomic dynamics across the SAT cell-types. We discovered that the SAT CG methylation (mCG) landscape is characterized by pronounced hyper-methylation in myeloid cells and hypo-methylation in adipocytes and adipose stem and progenitor cells (ASPCs), driving nearly half of the 705,063 detected differentially methylated regions (DMRs).

Exploring successes, barriers, and enablers in the one-year digital Healthy Weight Coaching.

Introduction: Healthcare professionals' perspectives are often overlooked in the evaluation of digital weight loss interventions. Thus, we examined how healthcare professionals perceive patient success in a one-year web-based weight management program, the Healthy Weight Coaching, aiming to identify key success factors and common challenges within the coaching process.

Methods: Thematic analysis was conducted on ten semi-structured interviews with healthcare professionals from the Healthy Weight Coaching.

Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome.

Decline in Isotope Dilution Space Ratio Above Age 60 Could Affect Energy Estimates Using the Doubly Labeled Water Method.

Background: Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training.

Subcutaneous adipose tissue and skeletal muscle mitochondria following weight loss.

Obesity is a major global health issue with various metabolic complications. Both bariatric surgery and dieting achieve weight loss and improve whole-body metabolism, but vary in their ability to maintain these improvements over time. Adipose tissue and skeletal muscle metabolism are crucial in weight regulation, and obesity is linked to mitochondrial dysfunction in both tissues.

An updated study protocol for a real-life digital 12-month weight management program, the Healthy Weight Coaching.

Obesity is an important health concern that poses many public health challenges. Evidence-based treatment modalities, capable of cost-effectively reaching large patient groups are needed. In this paper, we present the design and methods of the updated national, 12-month, digital weight management program, the Healthy Weight Coaching (HWC).

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.

Background: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes.

Methods: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L).

Loneliness and its cross-sectional associations with health, health behaviours, and perceptions in Finnish patients with overweight or obesity taking part in the Healthy Weight Coaching.

Objective: To investigate cross-sectional associations between loneliness and health, health behaviours, and perceptions in Finnish individuals with overweight or obesity (BMI ≥25 kg/m).

Methods: We used baseline data from patients participating, in 2016-2022, in a real-life digital 12-month weight management program known as Healthy Weight Coaching. Patients completed several questionnaires such as those related to loneliness, healthcare resource utilization, physical activity, and life satisfaction.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

Age-dependent genes in adipose stem and precursor cells affect regulation of fat cell differentiation and link aging to obesity via cellular and genetic interactions.

Background: Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner.

Metabolic syndrome and epigenetic aging: a twin study.

Background: Metabolic syndrome (MetS) is associated with premature aging, but whether this association is driven by genetic or lifestyle factors remains unclear.

Methods: Two independent discovery cohorts, consisting of twins and unrelated individuals, were examined (N = 268, aged 23-69 years). The findings were replicated in two cohorts from the same base population.

Mental, physical, and social well-being and quality of life in healthy young adult twin pairs discordant and concordant for body mass index.

Objective: The relationship between obesity and mental health is complex and is moderated by the level of obesity, age, sex, and social and genetic factors. In the current study, we used a unique co-twin control design, with twin pairs discordant for body mass index (BMI), to control for shared genetic and environmental effects between obesity and several dimensions of mental health.

Methods: We studied 74 monozygotic (MZ) twin pairs, of whom 36 were BMI-discordant (intra-pair difference in BMI ≥ 3 kg/m2), and 77 dizygotic (DZ) twin pairs (46 BMI-discordant).

Development and validation of a weight-loss predictor to assist weight loss management.

This study aims to develop and validate a modeling framework to predict long-term weight change on the basis of self-reported weight data. The aim is to enable focusing resources of health systems on individuals that are at risk of not achieving their goals in weight loss interventions, which would help both health professionals and the individuals in weight loss management. The weight loss prediction models were built on 327 participants, aged 21-78, from a Finnish weight coaching cohort, with at least 9 months of self-reported follow-up weight data during weight loss intervention.

Polygenic risk of obesity and BMI trajectories over 36 years: A longitudinal study of adult Finnish twins.

Objective: This study investigated 36-year BMI trajectories in twins whose BMI in young adulthood was below, within, or above their genetically predicted BMI, with a focus on twin pairs with large intrapair BMI differences (within-pair ΔBMI ≥ 3 kg/m ).

Methods: Together, 3227 like-sexed twin pairs (34% monozygotic) were examined at age ~30 years in 1975 and followed up in 1981, 1990, and 2011. An individual's observed BMI in 1975 was considered within (±2.

Roux-en-Y versus one-anastomosis gastric bypass (RYSA study): weight loss, metabolic improvements, and nutrition at 1 year after surgery, a multicenter randomized controlled trial.

Objective: Although it has been suggested that one-anastomosis gastric bypass (OAGB) is metabolically superior to the "gold standard," i.e., Roux-en-Y gastric bypass (RYGB), there is little robust evidence to prove it.

Human visceral adipose tissue microvascular endothelial cell isolation and establishment of co-culture with white adipocytes to analyze cell-cell communication.

Communication between adipocytes and endothelial cells (EC) is suggested to play an important role in the metabolic function of white adipose tissue. In order to generate tools to investigate in detail the physiology and communication of EC and adipocytes, a method for isolation of adipose microvascular EC from visceral adipose tissue (VAT) biopsies of subjects with obesity was developed. Moreover, mature white adipocytes were isolated from the VAT biopsies by a method adapted from a previously published Membrane aggregate adipocytes culture (MAAC) protocol.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

Aim: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight.

Cardiometabolic health in adults born with very low birth weight-a sibling study.

Background: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls.

Methods: VLBW-participants were matched with term-born, same-sex siblings.