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Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.

Objective: Adipose tissue is a specialized endocrine organ that is involved in modulating whole‐body energy homeostasis and expresses a specific subset of genes, which may play a role in adipose tissue metabolism. The aim of this study was to search for novel adipose tissue‐specific genes using a tissue panel of RNAseq expression profiles. Methods: RNAseq expression profiles from 53 human tissues were downloaded from the GTex database. SLC19A3 expression was analyzed by microarray or real‐time PCR in two sets of paired subcutaneous and omental adipose tissue samples, in two studies with adipose tissue from persons with high or low body mass index (BMI), in adipose tissue from patients who underwent weight loss with a very‐low caloric diet and during preadipocyte‐adipocyte differentiation. Results: The RNAseq‐based tissue distribution expression screen identified SLC19A3 (encoding the thiamine transporter 2) as adipose tissue‐specific. SLC19A3 expression was higher in subcutaneous compared with omental adipose tissue in both sample sets (p = 0.043 and p < 0.001). Preadipocyte differentiation towards adipocytes resulted in increased SLC19A3 gene expression (p = 0.018 or less at all‐time points). Subcutaneous adipose tissue expression of SLC19A3 was lower in persons with high BMI in both cohorts (p = 0.008, and p < 0.001) and increased during a weight‐loss intervention (p = 0.006). Conclusion: The specific adipose tissue expression pattern of SLC19A3, together with its regulation in obesity and during weight loss, indicate that it plays a key role in adipocyte metabolism. [ABSTRACT FROM AUTHOR]

Objective: Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study.Research Design and Methods: The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years).Results: During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003).Conclusions: These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk. [ABSTRACT FROM AUTHOR]

Aims: People with obesity are at risk for developing heart failure (HF), but little is known about the mechanistic pathways that link obesity with cardiac dysfunction. Methods and results: We included 2030 participants from the Swedish Obese Subjects study who received conventional obesity treatment. First‐time detection of HF was obtained by cross‐checking the study population with the Swedish National Patient Register and the Swedish Cause of Death Register. We also examined if atrial fibrillation and myocardial infarction as time‐dependent variables could predict incident HF The mean age of the study cohort was 48.7 years, and 28% were men. The mean body mass index at baseline was 40.1 kg/m2 and remained stable during a median follow‐up of 20.1 years. First‐time diagnosis of HF occurred in 266 of patients and was related to male sex, increasing age, greater waist–hip ratio, hypertension, higher cholesterol, diabetes mellitus, and elevated free thyroxine in univariable analysis. Estimated glomerular filtration rate was negatively related to HF risk. In multivariable analysis, atrial fibrillation, which is related to HF with preserved ejection fraction (HFpEF), and myocardial infarction, which is linked to HF with reduced ejection fraction (HFrEF), were strongly associated with incident HF with sub‐hazard ratios 3.75 (95% confidence interval: 2.72–5.18, P < 0.001) and 3.68 (95% confidence interval: 2.55–5.30, P < 0.001), respectively. Conclusions: Both atrial fibrillation and myocardial infarction as time‐dependent variables were independently and strongly related to incident HF in people with excess body fat, suggesting two main obesity‐related mechanistic pathways leading to either HFpEF or HFrEF. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to study the recovery from, and incidence of, work-restricting musculoskeletal pain after bariatric surgery compared with usual obesity care., Methods: Pain in different body regions was monitored using questionnaires in the nonrandomized, prospective, controlled Swedish Obese Subjects (SOS) study, which included 2007 participants treated with bariatric surgery and a matched control group of 2040 participants receiving usual obesity care at primary health care centers. Self-reported pain in the neck and shoulders, back, hips, knees, and ankles was captured from questionnaires administered at baseline and after 1, 2, 3, 4, 6, 8, 10, 15, and 20 years., Results: Compared with matched controls, bariatric surgery was associated with better recovery from baseline work-restricting knee and ankle pain in both the short (1-4 years) and long term (up to 20 years), as well as from back and hip pain in the short term. In participants without pain at baseline, bariatric surgery was associated with a lower incidence of developing new pain in the knee and ankle in the short and long term., Conclusions: Bariatric surgery was associated with better recovery from pain, primarily in weight-bearing joints, as well as with prevention of pain development in the knee and ankle compared with matched controls receiving usual obesity care., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: People with obesity and type 2 diabetes (T2D) have reduced life expectancy, partly explained by increased risk of cardiovascular diseases and cancer. Here, we examined whether 2-year diabetes remission after bariatric surgery or usual care is associated with long-term mortality., Materials and Methods: This report includes 586 participants with obesity and concomitant T2D from the prospective Swedish Obese Subjects (SOS) cohort study; 338 underwent bariatric surgery and 248 received usual obesity care. At inclusion, age was 37-60 years and BMI ≥34 kg/m2 in men and ≥38 kg/m2 in women. Median follow-up was 26.2 years (interquartile range 22.7-28.7). Diabetes status was determined using self-reported data on diabetes medication and in-study measures of blood glucose and HbA1c. The study was cross-linked to Swedish national registers for data on morbidity, death, and emigration., Results: Overall, 284 participants, 71.9% of surgery and 16.5% of usual care patients, were in remission at the 2-year examination. During follow-up, mortality rates were 16.6 deaths per 1000 person-years (95% CI:13.7-20.1) in the remission subgroup and 26.0 deaths per 1000 person-years (95% CI:22.2-30.4) in the non-remission subgroup (adjusted hazard ratio (HRadj)=0.71, 95% CI:0.54-0.95, P=0.019). The adjusted median life expectancy in the remission subgroup was 2.5 years (95% CI:0.3-4.7) longer than in the non-remission subgroup. Specifically, remission was associated with decreased cardiovascular mortality (sub-HRadj=0.54, 95% CI:0.35-0.85, P=0.008), but no detectable association with cancer mortality was found (sub-HRadj=1.06, 95% CI:0.60-1.86), P=0.841)., Conclusion: In this post-hoc analysis of data from the SOS study, patients who achieved short-term diabetes remission had increased life expectancy and decreased cardiovascular death over up to 32 years of follow-up. Future studies should confirm these findings., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)