International Journal of Obesity

Background and objectives Interleukin-27 (IL-27) is a multifaceted heterodimer cytokine that exerts both pro-inflammatory and anti-inflammatory effects under different physiological conditions. IL-27 signaling plays a role in promoting energy expenditure through enhanced thermogenesis. The objective of the study is to determine the functional role of IL-27 in regulating weight gain, and glucose and lipid homeostasis in mice fed a high-fat diet (HFD). Methods C57BL/6 mice were hydrodynamically transferred with pLIVE-IL-27 plasmids to achieve elevated level of IL-27 in blood and then kept on a HFD for 8 weeks. The impacts of Il-27 gene transfer on HFD-induced weight gain, adiposity, hepatic lipid accumulation, insulin resistance, glucose homeostasis and the mRNA levels of genes responsible for lipogenesis, glucose homeostasis and proinflammation were assessed by methods of biochemistry, histology, and molecular biology. Results Hydrodynamic gene transfer of Il-27 gene resulted in a peak level of serum IL-27 in mice at 14.5 ng/ml 24 h after gene transfer followed by a sustained level at 2 ng/ml. The elevated level of IL-27 blocked HFD-induced fat accumulation and weight gain without reducing food intake. It also prevented metabolic abnormities of liver steatosis and insulin resistance. IL-27 overexpression promoted expression of major thermogenic genes in brown adipose tissues; and attenuated chronic inflammation and macrophage infiltration into white adipose tissues. Conclusions The results demonstrate that regulation of IL-27 level could be an effective strategy for management of obesity and obesity-related metabolic diseases.

Aims Body weight loss improves insulin resistance and growth hormone secretion in obesity, which may be regulated by leptin according to preclinical studies. How changes in leptin, lipids and insulin sensitivity after bariatric (metabolic) surgery affect the human growth hormone system is yet unclear. Participants and methods People with obesity (OBE, n = 79, BMI 50.8 ± 6.3 kg/m²) were studied before, 2, 12, 24 and 52 weeks after metabolic surgery and compared to lean healthy humans (control; CON, n = 24, BMI 24.3 ± 3.1 kg/m²). Tissue-specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps with D-[6,6-²H2]glucose. Fasting leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and IGF-binding proteins (IGFBP1, IGFBP3) were measured using ELISA. Results At baseline, OBE exhibited higher glycemia and leptinemia as well as pronounced peripheral, adipose tissue and hepatic insulin resistance compared to CON. GH and IGFBP1 were lower, while IGF1 was comparable between groups. At 52 weeks, OBE had lost 33% body weight and doubled their peripheral insulin sensitivity, which was paralleled by continuous increases in GH, IGF-1 and IGFBP1 as well as decrease in leptin. The rise in GH correlated with reductions in free fatty acids, adipose tissue insulin resistance and insulinemia, but not with changes in body weight, peripheral insulin sensitivity, glycemia or leptinemia. The rise in IGF-1 correlated with reduction in high-sensitive C-reactive protein. Conclusion Reversal of alterations of the GH-IGF-1 axis after surgically-induced weight loss is unlikely related to improved leptin secretion and/or insulin sensitivity, but is rather associated with restored adipose tissue function and reduced low-grade inflammation.

Background Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether these associations reflect causal relationships. Methods We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumour gastrointestinal diseases. The inverse-variance weighted method was used to perform the MR analyses. Complementary and multivariable MR analyses were performed to confirm the results. Results Genetically predicted higher VAT was associated with an increased risk of gastro-oesophageal reflux disease (GORD) (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09–1.34; P = 3.06 × 10⁻⁴), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10–1.77; P = 0.005), cholelithiasis (OR, 1.75; 95% CI, 1.53–2.00; P = 1.14 × 10⁻¹⁶), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87–3.82; P = 6.26 × 10⁻⁸). There were suggestive associations between VAT and gastric ulcer (GU) (OR, 1.22; 95% CI, 1.01–1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05–1.52; P = 0.013). However, there was little evidence to support the associations between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. The associations with GORD, GU, and NAFLD remained in the multivariable MR analyses with adjustment for body mass index (BMI). Conclusions This study provided evidence in support of causal associations between VAT and GORD, GU, DU, cholelithiasis, AP, and NAFLD. Moreover, the associations between GORD, GU, and NAFLD were independent of the effect of BMI.

Background Previous studies demonstrated a relation between takeaway outlet exposure and health outcomes. Individual characteristics, such as eating behaviour traits, could make some people more susceptible to the influence of the food environment. Few studies have investigated this topic. We aimed to investigate the moderating role of eating behaviour traits (cognitive restraint, uncontrolled eating and emotional eating) in the association between neighbourhood exposure to hot food takeaway outlets (hereafter referred to as takeaway outlets), and takeaway food consumption and adiposity. Methods We used cross-sectional data from a cohort in Cambridgeshire, UK (The Fenland study). Takeaway outlet exposure was derived using participants’ residential address and data from local authorities and divided into quarters. The Three Factor Eating questionnaire (TFEQ-R18) was used to measure eating behaviour traits. Primary outcomes were consumption of takeaway-like foods (derived from food frequency questionnaire), and body fat percentage (measured using dual-energy X-ray absorptiometry). Results Mean age of participants (n = 4791) was 51.0 (SD = 7.2) and 53.9% were female. Higher exposure to takeaway outlets in the neighbourhood and higher eating behaviour trait scores were independently associated with greater takeaway consumption and body fat percentage. Uncontrolled eating did not moderate the associations between takeaway outlet exposure and takeaway consumption or body fat percentage. The association between takeaway outlet exposure and takeaway consumption was slightly stronger in those with higher cognitive restraint scores, and the association between takeaway outlet exposure and body fat percentage was slightly stronger in those with lower emotional eating scores. Conclusion Eating behaviour traits and exposure to takeaway outlets were associated with greater takeaway consumption and body fat, but evidence that individuals with certain traits are more susceptible to takeaway outlets was weak. The findings indicate that interventions at both the individual and environmental levels are needed to comprehensively address unhealthy diets. Trial registry ISRCTN72077169

Background Obesity is major cause of cardiovascular diseases. Metabolically healthy obesity (MHO) may increase heart failure risk early in life, and may be reflected in impaired cardiac structure and function. Therefore, we aimed to examine the relationship between MHO in young adulthood and cardiac structure and function. Methods A total of 3066 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were included, who completed echocardiography in young adulthood and middle age. The participants were grouped by obesity status (body mass index ≥30 kg/m²) and poor metabolic health (≥2 criteria for metabolic syndrome) into four metabolic phenotypes as follows: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). The associations of the metabolic phenotypes (MHN serving as the reference) with left ventricular (LV) structure and function were evaluated using multiple linear regression models. Results At baseline, mean age was 25 years, 56.4% were women, and 44.7% were black. After a follow-up 25 years, MUN in young adulthood was associated with worse LV diastolic function (E/é ratio, β [95% CI], 0.73 [0.18, 1.28]), worse systolic function (global longitudinal strain [GLS], 0.60 [0.08, 1.12]) in comparison with MHN. MHO and MUO were associated with LV hypertrophy (LV mass index, 7.49 g/m² [4.63, 10.35]; 18.23 g/m² [12.47, 23.99], respectively), worse diastolic function (E/é ratio, 0.67 [0.31, 1.02]; 1.47 [0.79, 2.14], respectively), and worse systolic function (GLS, 0.72 [0.38, 1.06]; 1.35 [0.64, 2.05], respectively) in comparison with MHN. These results were consistent in several sensitivity analyses. Conclusions In this community-based cohort using data from the CARDIA study, obesity in young adulthood was significantly associated with LV hypertrophy, worse systolic and diastolic function regardless of metabolic status. Relationship of Baseline Metabolic Phenotypes with Young Adulthood and Midlife Cardiac Structure and Function. Adjusted for year 0 covariates: age, sex, race, educational level, smoking status, drinking status, and physical activity; metabolically healthy non-obesity was used as a reference category for comparison. † Criteria for metabolic syndrome are listed in Supplementary Table S6. MUN metabolically unhealthy non-obesity, MHO metabolically healthy obesity, LVMi left ventricular mass index, LVEF left ventricular ejection fraction, E/A early to late peak diastolic mitral flow velocity ratio, E/é mitral inflow velocity to early diastolic mitral annular velocity, CI confidence interval.

Background There is growing evidence that internet-delivered cognitive behavioural therapy (iCBT) can improve functioning and reduce psychological distress in people with chronic health conditions. Obesity frequently co-occurs with chronic health conditions, yet its impact on response to psychological interventions in this population is not known. The current study examined associations between BMI and clinical outcomes (depression, anxiety, disability, and satisfaction with life) following a transdiagnostic iCBT program targeting adjustment to chronic illness. Methods Participants from a large randomised controlled trial, who provided information on height and weight, were included (N = 234; mean age= 48.32, SD = 13.80; mean BMI = 30.43, SD = 8.30, range 16.18–67.52; 86.8% female). The influence of baseline BMI range on treatment outcomes at post-treatment and 3-month follow-up was examined using generalized estimating equations. We also examined changes in BMI and in participants’ perceived impact of weight on their health. Results Improvement in all outcomes occurred across BMI ranges; additionally, persons with obesity or overweight generally experienced greater symptom reductions than those within a healthy weight range. A greater proportion of participants with obesity achieved clinically significant change on key outcomes (e.g., depression: 32% [95% CI: 25%, 39%]) than participants with a healthy weight (21% [95% CI: 15%, 26%]) or overweight (24% [95% CI: 18%, 29%], p = 0.016). There were no significant changes in BMI from pre-treatment to 3-month follow-up, however there were significant reductions on the self-rated impact of weight on health. Conclusions Persons with chronic health conditions and with obesity or overweight benefit at least as much as those with a healthy BMI from iCBT programs targeting psychological adjustment to chronic illness, even without changes in BMI. iCBT programs may be an important component in the self-management of this population, and may address barriers implicated in health behaviour change.

Background Accumulating evidence suggests that pneumonia mortality is lower for individuals with high body mass index (BMI) compared to normal BMI, but it remains unclear whether weight change during adulthood influences subsequent mortality due to pneumonia in Asian populations, who have a relatively lean body mass. This study aimed to examine the association of BMI and weight change over 5 years with the subsequent risk of pneumonia mortality in a Japanese population. Methods The present analysis included 79,564 Japan Public Health Center (JPHC)-based Prospective Study participants who completed a questionnaire between 1995 and 1998 were followed for death through 2016. BMI was categorized into four groups: underweight (<18.5 kg/m²), normal weight (BMI: 18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (BMI: ≥30.0 kg/m²). Weight change was defined as the difference of body weight between questionnaire surveys with a 5-year interval. Cox proportional hazards regression was used to estimate hazard ratios of baseline BMI and weight change for pneumonia mortality. Results During a median follow-up of 18.9 y, we identified 994 deaths from pneumonia. Compared with participants with normal weight, an elevated risk was observed among those who were underweight (hazard ratio = 2.29, 95% confidence interval [CI]: 1.83–2.87), whereas a decreased risk was found among those who were overweight (hazard ratio = 0.63, 95% CI: 0.53–0.75). Regarding weight change, the multivariable-adjusted hazard ratio (95% CI) of pneumonia mortality for a weight loss of 5 kg or more versus a weight change of less than 2.5 kg was 1.75 (1.46–2.10), whereas that for a weight gain of 5 kg or more was 1.59 (1.27–2.00). Conclusion Underweight and greater weight change was associated with an increase in the risk of pneumonia mortality in Japanese adults.

Background The resistin/uric index has been considered a prognostic factor for identifying young people with obesity. Obesity and Metabolic Syndrome (MS) are an important health problem in females. Aims The objective of this work was to evaluate the relationship of resistin/acid uric index with Metabolic Syndrome on Caucasian females with obesity. Methods We conducted a cross sectional study in 571 females with obesity. Measurements of anthropometric parameters, blood pressure, fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), lipid profile, C reactive protein, uric acid, resistin and prevalence of Metabolic Syndrome were determined. The resistin/uric acid index was calculated. Results In total, 249 subjects had MS (43.6%). We detected higher levels in the following parameters (Delta; p values); waist circumference (3.1 ± 0.5 cm; p = 0.04), systolic blood pressure (5.3 ± 3.6 mmHg; p = 0.01), diastolic blood pressure (2.3 ± 0.4 mmHg; p = 0.02), glucose levels (7.5 ± 0.9 mg/dL; p = 0.01), insulin levels (2.5 ± 0.3 UI/L; p = 0.02), HOMA-IR (0.7 ± 0.2 units; p = 0.03), uric acid levels (0.9 ± 0.2 mg/dl; p = 0.01), resistin levels (4.1 ± 0.4 ng/dl; p = 0.01) and resistin/uric acid index (0.61 ± 0.01 mg/dl; p = 0.02) in subjects of the high resistin/uric acid index group than low index group. Logistic regression analysis reported a high percentage of hyperglycemia (OR = 1.77, 95% CI = 1.10–2.92; p = 0.02), hypertension (OR = 1.91, 95% CI = 1.36–3.01; p = 0.01), central obesity (OR = 1.48, 95% CI = 1.15–1.84; p = 0.03) and metabolic syndrome percentage (OR = 1.71, 95% CI = 1.22–2.69; p = 0.02) in high resistin/uric acid index group. Conclusions Resistin/uric acid index is related with Metabolic syndrome (MS) risk and criteria of it in a population of Caucasian females with obesity and this index is a correlated with glucose levels, insulin levels and insulin resistance (HOMA-IR).

Background/Objectives Weight gain is a barrier to smoking cessation. Previous interventions targeting weight gain while quitting smoking have largely been unsuccessful. The current study aimed to assess the efficacy of weight stability and weight loss interventions compared to a low-intensity, self-guided bibliotherapy weight management group. Subjects/Methods A randomized controlled trial with 12-month follow-up from 2018 to 2022 was conducted with participants (N = 305) who reported smoking at least five cigarettes per day for the last year and interest in quitting initially recruited from the Memphis, TN, USA area. Recruitment was expanded nationally with the onset of the COVID-19 pandemic. Subsequently, 276 completed 12-month follow-up. Interventions/Methods The Bibliotherapy group was provided a weight management book. Both the Stability and Loss groups met via telephone for eight weeks to learn strategies for maintaining/losing weight, respectively. All three groups then received the same six-week smoking cessation intervention, with six months of varenicline provided. Results Individuals in the Loss group lost more weight (−2.01 kg, SE = 1.58) than individuals in the Bibliotherapy group (+1.08 kg, SE = 1.49, p = 0.0004), while the Stability group (−0.30 kg, SE = 1.56) was not significantly different from the Bibliotherapy group (p = 0.17). Those in the Stability group did not gain a significant amount of weight. Participants in the Loss group did not gain back all weight lost after smoking cessation and ended the study approximately 2.01 kg lower than baseline. The Bibliotherapy group did not gain the amount of weight expected after cessation. There were no significant differences between groups related to self-reported smoking cessation at each time point except at eight-month follow-up (p = 0.005). Conclusions and relevance Results indicated the Stability and the Loss interventions were effective for preventing post-smoking cessation weight gain, with the Loss group having the benefit of sustained weight loss. These interventions may be helpful to implement to combat weight gain and potentially facilitate smoking cessation. Trial Registration The trial is registered on clinicaltrials.gov (NCT03156660).

The effect of exercise training on whole-body insulin sensitivity has not been systematically summarized. We aimed to summarize the data from randomized controlled trials evaluating the effect of exercise training on insulin action, in adults. MEDLINE, EMBASE, and CENTRAL databases were searched until January 2021. Randomized controlled trials lasting ≥4 weeks, including adults, and evaluating the effect of exercise on insulin-stimulated glucose disposal measured using the hyperinsulinemic euglycemic clamp, were included. Three reviewers extracted summary data from published trials. The primary outcome was insulin-stimulated glucose disposal. Standardized weighted mean differences (SMD) in glucose disposal between intervention and control were compared. The PEDro scale was used to assess risk of bias. We included 25 trials (36 interventions, N = 851). Exercise increased insulin-stimulated glucose disposal relative to control, SMD = 0.52 (95% confidence interval [CI]: 0.39, 0.65; p < 0.001; I2 = 47%) without significantly suppressing hepatic glucose production. In trials without isotopic tracers, exercise increased glucose disposal (SMD = 0.63; 95% CI: 0.48, 0.77; p < 0.001, I2 = 55%). In trials with isotopic tracers, exercise increased glucose disposal only when tracers were added to the exogenous glucose used for clamping (SMD = 0.34; 95% CI: 0.03, 0.66, p = 0.034. I2 = 0%). In a meta-regression model including aerobic exercise, weight change, and tracer technique, only percent weight change explained between trial heterogeneity (β = 0.069; 95% CI: 0.005, 0.013). The PEDro rating indicated relatively low risk of bias (5.8 ± 0.22). Exercise training for at least four weeks significantly increases insulin-stimulated glucose disposal. Weight loss maximizes the effect and may be needed to improve hepatic insulin sensitivity. Differences in tracer methodology contribute to divergent outcomes and should be considered when assessing conclusions from research examining the effect of exercise on insulin action. PROSPERO (CRD42019124381).

Background Increasing physical activity and limiting sedentary time may minimize weight recurrence after bariatric surgery. However, few studies have evaluated potential associations of objectively-measured physical activity and sedentary time with post-surgical weight recurrence over time. Aims To evaluate associations of change in physical activity and sedentary time with weight recurrence after bariatric surgery. Methods Participants from the Oslo Bariatric Surgery Study, a prospective cohort study, wore an ActiGraph monitor for seven days at 1- and 5 years after surgery to assess daily physical activity and sedentary time. Participants’ weight was measured at in-person clinic visits. Chi-square Test and Paired-samples T-test evaluated group differences and change over time, while Pearson’s Correlation, multiple logistic and linear regression investigated associations between variables. Results Five years after surgery 79 participants (70.5% response rate, 81% female) (mean (sd) age: 54.0 (±9.3), BMI: 32.1 (±4.7)) had valid monitor data. Participants increased their sedentary time (71.4 minutes/day (95% CI: 54.2–88.6, p = <0.001)) and reduced daily steps (−1411.1 (95% CI: 737.8–208.4), p = <0.001), light physical activity (−54.1 min/day (95% CI: 40.9–67.2, p = <0.001)), and total physical activity (−48.2 (95% CI: 34.6–63.3), p = <0.001) from 1- to 5 years after surgery. No change was found for moderate-to-vigorous intensity physical activity. No associations were found between changes in steps, physical activity or sedentary time and weight recurrence. Conclusion Participants increased sedentary time and decreased light- and total physical activity between 1- and 5 years post-surgery. Overall, changes in physical activity and sedentary time were not associated with weight recurrence. Interventions to help patients increase physical activity and limit sedentary time after bariatric surgery are needed.

Background/Objective This observational study dissects the complex temporal associations between body-mass index (BMI), waist-hip ratio (WHR) and circulating metabolomics using a combination of longitudinal and cross-sectional population-based datasets and new systems epidemiology tools. Subjects/Methods Firstly, a data-driven subgrouping algorithm was employed to simplify high-dimensional metabolic profiling data into a single categorical variable: a self-organizing map (SOM) was created from 174 metabolic measures from cross-sectional surveys (FINRISK, n = 9708, ages 25–74) and a birth cohort (NFBC1966, n = 3117, age 31 at baseline, age 46 at follow-up) and an expert committee defined four subgroups of individuals based on visual inspection of the SOM. Secondly, the subgroups were compared regarding BMI and WHR trajectories in an independent longitudinal dataset: participants of the Young Finns Study (YFS, n = 1286, ages 24–39 at baseline, 10 years follow-up, three visits) were categorized into the four subgroups and subgroup-specific age-dependent trajectories of BMI, WHR and metabolic measures were modelled by linear regression. Results The four subgroups were characterised at age 39 by high BMI, WHR and dyslipidemia (designated TG-rich); low BMI, WHR and favourable lipids (TG-poor); low lipids in general (Low lipid) and high low-density-lipoprotein cholesterol (High LDL-C). Trajectory modelling of the YFS dataset revealed a dynamic BMI divergence pattern: despite overlapping starting points at age 24, the subgroups diverged in BMI, fasting insulin (three-fold difference at age 49 between TG-rich and TG-poor) and insulin-associated measures such as triglyceride-cholesterol ratio. Trajectories also revealed a WHR progression pattern: despite different starting points at the age of 24 in WHR, LDL-C and cholesterol-associated measures, all subgroups exhibited similar rates of change in these measures, i.e. WHR progression was uniform regardless of the cross-sectional metabolic profile. Conclusions Age-associated weight variation in adults between 24 and 49 manifests as temporal divergence in BMI and uniform progression of WHR across metabolic health strata.

Background Bardet–Biedl syndrome (BBS) is a rare autosomal recessive syndromic obesity of childhood onset among many other features. To date, the excess risk of metabolic complications of severe early-onset obesity in BBS remains controversial. In-depth investigation of adipose tissue structure and function with detailed metabolic phenotype has not been investigated yet. Objective To investigate adipose tissue function in BBS. Design A prospective cross-sectional study. Main outcome measure To determine if there are differences in insulin resistance, metabolic profile, adipose tissue function and gene expression in patients with BBS compared to BMI-matched polygenic obese controls. Method 9 adults with BBS and 10 controls were recruited from the national centre for BBS, Birmingham, UK. An in-depth study of adipose tissue structure and function along with insulin sensitivity was performed using hyperinsulinemic-euglycemic clamp studies, adipose tissue microdialysis, histology and RNA sequencing, and measurement of circulating adipokines and inflammatory biomarkers. Results Adipose tissue structure, gene expression and in vivo functional analysis between BBS and polygenic obesity cohorts were similar. Using hyperinsulinemic-euglycemic clamp and surrogate markers of insulin resistance, we found no significant differences in insulin sensitivity between BBS and obese controls. Furthermore, no significant changes were noted in an array of adipokines, cytokines, pro-inflammatory markers and adipose tissue RNA transcriptomic. Conclusion Although childhood-onset extreme obesity is a feature of BBS, detailed studies of insulin sensitivity and adipose tissue structure and function are similar to common polygenic obesity. This study adds to the literature by suggesting that it is the quality and quantity of adiposity not the duration that drives the metabolic phenotype.

Background The globally high prevalence of both obesity and bipolar disorder makes the bidirectional relationship between the two disorders a pivotal phenomenon; hence, a meta-analysis to synopsize their co-occurrence is indispensable. Psychotropic-induced obesity has been reported to be an important factor linking bipolar disorder and obesity. Nonetheless, the molecular signature of this connection is perplexing. Methods Here, we leverage both meta-analysis and bioinformatics analysis to provide a conspectus and deduce the molecular signature of obesity in bipolar disease patients following psychotropic treatment. Searches were performed on a diverse collection of databases through June 25, 2020. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Analysis of OR, 95% CI, and tests of homogeneity were carried out with STATA software. For the bioinformatics analysis, the LIMMA package which is incorporated into the Gene Expression Omnibus database was used. Results Our search yielded 138 studies, of which 18 fitted our inclusion criteria. Individuals who are obese have an increased risk of developing bipolar disorder (pooled adjusted OR = 1.32, 95% CI = 1.01–1.62). In a manner analogous to this, the pooled adjusted odds ratio reveals that patients with bipolar disorder have an increased chance of obesity (OR = 1.68, 95% CI = 1.35–2). To deduce the molecular signature of obesity in bipolar disorder patients following psychotropic treatment, three data sets from the Gene Expression Omnibus database (GSE5392, GSE87610, and GSE35977) were integrated and the genes obtained were validated by a cohort of known single nucleotide polymorphism of obesity via direct overlap. Results indicate genes that are activated after psychotropic treatment. Some of these genes are CYBB, C3, OLR1, CX3CR1, C3AR1, CD53, AIF1, LY86, BDNF, ALOX5AP, CXCL10, and the preponderance falls under mesodermal and PI3K-Akt signaling pathway. The ROC analysis reveals a strong discriminating value between the two groups (UBAP2L AUC = 0.806, p = 1.1e-04, NOVA2 AUC = 0.73, p = 6.7e-03). Conclusion Our study shows unequivocal evidence of a bi-directional association between bipolar disorder and obesity, but more crucially, it provides a snapshot of the molecular signature of obesity in bipolar patients as a result of psychotropic medication.

Background Genome-wide association studies have shown that body mass index (BMI), an estimate of obesity, is highly polygenic. Individual variants typically have small effect sizes, making it challenging to identify unique loci in under-represented ethnic groups which lack statistical power due to their small sample size. Yet obesity is a major health disparity and is particularly prevalent in southwestern American Indians. Here, we identify and characterize a new locus for BMI that was detected by analyzing moderate associations with BMI obtained in a population-based sample of southwestern American Indians together with the well-powered GIANT dataset. Methods Genotypes for 10.5 million variants were tested for association with BMI in 5870 American Indians and 2600 variants that showed an association P < 10⁻³ in the American Indian sample were combined in a meta-analysis with the BMI data reported in GIANT (N = 240,608). The newly identified gene, NFIA-AS2 was functionally characterized, and the impact of its lead associated variant rs1777538 was studied both in-silico and in-vitro. Results Rs1777538 (T/C; C allele frequency = 0.16 in American Indians and 0.04 in GIANT, meta-analysis P = 5.0 × 10⁻⁷) exhibited a large effect in American Indians (1 kg/m² decrease in BMI per copy of C allele). NFIA-AS2 was found to be a nuclear localized long non-coding RNA expressed in tissues pertinent to human obesity. Analysis of this variant in human brown preadipocytes showed that NFIA-AS2 transcripts carrying the C allele had increased RNA degradation compared to the T allele transcripts (half-lives = 9 h, 13 h respectively). During brown adipogenesis, NFIA-AS2 featured a stage-specific regulation of nearby gene expression where rs1777538 demonstrated an allelic difference in regulation in the mature adipocytes (the strongest difference was observed for L1TD1, P = 0.007). Conclusion Our findings support a role for NFIA-AS2 in regulating pathways that impact BMI.

Background Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors. Methods Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes. Results Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (β = 3.85, 95% CI 1.22–6.49, P = 0.004) and a decrease in adiponectin level (β = −0.04, 95% CI −0.06 to −0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA. Conclusions The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic.

Background Obesity is rapidly increasing in Mexican children and adolescents, while food environments are rapidly changing. We evaluated the association between changes in retail food stores and change in body mass index (BMI) in Mexican children and adolescents. Methods Data on 7507 participants aged 5–19 years old came from the Mexican Family Life Survey 2002–2012. Density of food stores at the municipal-level (number of food stores/area in km²) came from the Economic Censuses of 1999, 2004 and 2009. We categorized food stores as small food retail (small neighborhood stores, tiendas de abarrotes in Mexico), specialty foods, fruit/vegetables, convenience foods, and supermarkets. Associations between change in food stores and change in BMI were estimated using five longitudinal linear fixed-effects regression models (one per type of food store) adjusted for age, parental education, municipal-level socioeconomic deprivation and population density. Density of each food store type was operationalized as quartiles. Analyses were stratified by urbanization. Results There was an inverse dose-response association between increases in fruit/vegetable store density and BMI (β = −0.455 kg/m², β = −0.733 kg/m², and β = −0.838 kg/m² in the second, third, and fourth quartile). In non-urban areas, children living in municipalities with the highest density of small food retail stores experienced a reduction in BMI (β = −0.840 kg/m²). In urban areas, there was an inverse association between specialty food stores with BMI (β = −0.789 kg/m² in third quartile, and β = −1.204 kg/m² in fourth quartile). We observed dynamic associations with age; results suggested stronger associations in adolescents. Conclusions The availability of fruit/vegetable stores may influence a reduction in children and adolescents BMI. These results indicate that policy approaches could be tailored by type of food store – with some consideration for level of urbanization and children’s age.

Background How obesity earlier in life impacts upon mobility dysfunctions in late life is not well understood. Pernicious effects of excess weight on the musculoskeletal system and mobility dysfunctions are well-recognized. However, increasingly more data support the link of obesity to overall motor defects that are regulated in the brain. Objectives To assess the causal relationship between body mass index (BMI) at midlife and performance of the Timed Up-and-Go test (TUG) in late life among a population-based longitudinal cohort of Chinese adults living in Singapore. Methods We evaluated genetic predispositions for BMI in 8342 participants who were followed up from measurement of BMI at average 53 years, to TUG test (as a functional mobility measure) 20 years later. Results A robust 75.83% of genetically determined BMI effects on late-life TUG scores were mediated through midlife BMI (Pindirect-effect = 9.24 × 10⁻²¹). Utilizing Mendelian randomization, we demonstrated a causal effect between BMI and functional mobility in late life (βIVW = 0.180, PIVW = 0.001). Secondary gene enrichment evaluations highlighted down-regulation of genes at BMI risk loci that were correlated with poorer functional mobility in the substantia nigra and amygdala regions as compared to all other tissues. These genes also exhibit differential expression patterns during human brain development. Conclusions We report a causal effect of obesity on mobility dysfunction. Our findings highlight potential neuronal dysfunctions in regulating predispositions on the causal pathway from obesity to mobility dysfunction.

Background It is established that pulmonary disorders are comorbid with metabolic disorders such as obesity. Previous studies show that the stimulator of interferon genes (STING) signaling plays crucial roles in obesity-induced chronic inflammation via TANK-binding kinase 1 (TBK1) pathways. However, it remains unknown whether and how the STING signaling is implicated in the inflammatory processes in the lung in obesity. Methods Human lung tissues were obtained from obese patients (n = 3) and controls (n = 3). Mice were fed with the high-fat diet or regular control diet to establish the diet-induced obese (DIO) and lean mice, and were treated with C-176 (a specific STING inhibitor) or vehicle respectively. The lung macrophages were exposed to palmitic acid (PA) in vitro. The levels of STING singaling and metabolic inflammation factors were detected and anlyzed. Results We find that STING⁺/CD68⁺ macrophages are increased in lung tissues in patients with obesity. Our data also show that the expressions of STING and the levels of proinflammatory cytokines are increased both in lung tissues and bronchoalveolar lavage fluid (BALF) in obesity compared to controls, and inhibition of the STING blunted the obesity-induced lung inflammation. Mechanistically, our data demonstrate that the STING signaling pathway is involved in the PA-induced inflammation through the STING-TBK1-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) pathways in the lung macrophages. Conclusions Our results collectively suggest that the STING signaling contributes to obesity-associated inflammation by stimulating proinflammatory processes in lung macrophages, one that may serve as a therapeutic target in ameliorating obesity-related lung dysfunctions.

Background Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases. Aim To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle. Methods Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male). Results In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to β-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration. Conclusions Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes.

Objective To explore the prevalence of obesity among American Indian and Alaska Native (AIAN) adolescents aged 12–19 years in association with social determinants of health (SDOH), and mental health and substance use disorders. Methods Guided by the World Health Organization’s Social Determinants of Health Framework, we examined data from the Indian Health Service (IHS) Improving Health Care Delivery Data Project from Fiscal Year 2013, supplemented by county-level data from the U.S. Census and USDA. Our sample included 26,226 AIAN adolescents ages 12–19 years. We described obesity prevalence in relationship to SDOH and adolescents’ mental health and substance use disorder status. We then fit a multivariable logit generalized linear mixed model to estimate the relationships after adjusting for other individual and county level characteristics. Results We observed a prevalence of 32.5% for obesity, 13.8% for mental health disorders, and 5.5% for substance use disorders. Females had lower odds of obesity than males (OR = 0.76, p < 0.001), which decreased with age. Having Medicaid coverage (OR = 1.09, p < 0.01), residing in a county with lower education attainment (OR = 1.17, p < 0.05), and residing in a county with higher rates of poverty (OR = 1.51, p < 0.001) were each associated with higher odds of obesity. Residing in a county with high access to a grocery store (OR = 0.73, p < 0.001) and residing in a county with a higher proportion of AIANs (OR = 0.83, p < 0.01) were each associated with lower odds of obesity. Those with mental health disorders had higher odds of obesity (OR = 1.26, p < 0.001); substance use disorders were associated with decreased odds of obesity (OR = 0.73, p < 0.001). Conclusions Our findings inform future obesity prevention and treatment programs among AIAN youth; in particular, the need to consider mental health, substance use, and SDOH.

Background/Objectives To evaluate anthropometric measures for the prediction of whole-abdominal adipose tissue volumes VXAT (subcutaneous VSAT, visceral VVAT and total VTAT) in patients with obesity. Subjects/Methods A total of 181 patients (108 women) with overweight or obesity were analyzed retrospectively. MRI data (1.5 T) were available from independent clinical trials at a single institution (Integrated Research and Treatment Center of Obesity, University of Leipzig). A custom-made software was used for automated tissue segmentation. Anthropometric parameters (AP) were circumferences of the waist (WC) and hip (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and the (hypothetical) hip-to-height ratio (HHtR). Agreement was evaluated by standard deviations sd% of percent differences between estimated volumes (using results of linear AP–VXAT regression) and measured ones as well as Pearson’s correlation coefficient r. Results For SAT volume estimation, the smallest sd% for all patients was seen for HC (25.1%) closely followed by HHtR (25.2%). Sex-specific results for females (17.5% for BMI and 17.2% for HC) and males (20.7% for WC) agreed better. VAT volumes could not be estimated reliably by any of the anthropometric measures considered here. TAT volumes in a mixed population could be best estimated by BMI closely followed by WC (roughly 17.5%). A sex-specific consideration reduced the deviations to around 16% for females (BMI and WC) and below 14% for males (WC). Conclusions We suggest the use of sex-specific parameters–BMI or HC for females and WC for males–for the estimation of abdominal SAT and TAT volumes in patients with overweight or obesity.

Background Abdominal adiposity, including visceral and subcutaneous abdominal adipose tissue (VAT and SAT), is recognized as a strong risk factor for cardiometabolic disease, cancer, and mortality. Objective The primary aim of this analysis is to describe longitudinal patterns of change in abdominal adipose tissue in postmenopausal women, overall and stratified by age, race/ethnicity, and years since menopause. Methods The data are from six years of follow up on 10,184 postmenopausal women (7828 non-Hispanic White women, 1423 non-Hispanic Black women, and 703 Hispanic women) who participated in the Women’s Health Initiative (WHI). The WHI is a large prospective cohort study of postmenopausal women across the United States. All participants in this analysis had DXA scans in the 1990s as part of the WHI protocol. Hologic APEX software was used to re-analyze archived DXA scans and obtain measures of abdominal adipose tissue. Analyses examined differences in abdominal adipose tissue, overall adiposity, and anthropometric variables. Results There were important differences in VAT and SAT by age and race/ethnicity. In women <60 years, VAT increased over the follow-up period, while in women ≥70 years, VAT decreased. Non-Hispanic Black women had the highest levels of SAT. Hispanic women had the highest VAT levels. Women more than ten years since menopause had less SAT and more VAT than women less than ten years since menopause, resulting in a higher VAT/SAT ratio. There was a moderate to strong correlation between measures of abdominal adipose tissue and anthropometric measurements of body size. Still, there were substantial differences in the quantity of VAT and SAT within BMI and waist circumference categories. Conclusions These results demonstrate differences in VAT and SAT according to age, race/ethnicity, time since menopause, and compared to standard measures of body composition in a large and diverse cohort of postmenopausal women.

Background: Rapid growth and excess weight in early childhood are associated with obesity risk. While maternal preconception BMI has been identified as a potential risk factor, the role of paternal preconception BMI is less clear. Objectives: To examine the association between paternal preconception BMI and age- and sex-standardized WHO BMI z-score (zBMI) growth rates, zBMI, and weight status, in 0- to 10-year-old children. To determine whether these associations differed by child sex and maternal preconception weight status. Methods: A longitudinal cohort study was conducted through The Applied Research Group for Kids (TARGet Kids!). Children (n = 218) underwent repeated measures of height and weight from birth to 10 years old. Piecewise linear mixed models were used to assess the association between paternal preconception BMI and child zBMI growth rates (zBMI SD units/month) between 0, 4, 30, 48 and 120 months of age. Linear mixed models were used to examine the association with child zBMI, and logistic generalized estimation equations (GEE) were used to assess the association with child weight status. Child sex and maternal preconception weight status were tested as effect modifiers. Results: Paternal preconception BMI was associated with child zBMI growth rate, mean zBMI and weight status in boys, but not girls. A 5 kg/m2 higher paternal preconception BMI was associated with approximately 0.01 zBMI SD unit/month higher growth rate for boys born to mothers with preconception overweight. Higher paternal BMI was associated with higher mean zBMI and increased odds of overweight and obesity in boys, with greater effects seen when mothers had preconception overweight compared to normal weight. Conclusion: Paternal preconception BMI was associated with child zBMI growth rate, zBMI and weight status in boys, with greater effects when the biological mother had preconception overweight or obesity. Further understanding of sex differences in paternal preconception weight effects in children is needed.

Objectives Studies in mice have recently linked increased dietary choline consumption to increased incidence of obesity-related metabolic diseases, while several clinical trials have reported an anti-obesity effect of high dietary choline intake. Since the underlying mechanisms by which choline affects obesity are incompletely understood, the aim of the present study was to investigate the role of dietary choline supplementation in adiposity. Methods Female APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism and cardiometabolic diseases, were fed a Western-type diet supplemented with or without choline (1.2%, w/w) for up to 16 weeks. Results Dietary choline reduced body fat mass gain, prevented adipocyte enlargement, and attenuated adipose tissue inflammation. Besides, choline ameliorated liver steatosis and damage, associated with an upregulation of hepatic genes involved in fatty acid oxidation. Moreover, choline reduced plasma cholesterol, as explained by a reduction of plasma non-HDL cholesterol. Mechanistically, choline reduced hepatic VLDL-cholesterol secretion and enhanced the selective uptake of fatty acids from triglyceride-rich lipoprotein (TRL)-like particles by brown adipose tissue (BAT), consequently accelerating the clearance of the cholesterol-enriched TRL remnants by the liver. Conclusions In APOE*3-Leiden.CETP mice, dietary choline reduces body fat by enhancing TRL-derived fatty acids by BAT, resulting in accelerated TRL turnover to improve hypercholesterolemia. These data provide a mechanistic basis for the observation in human intervention trials that high choline intake is linked with reduced body weight.

Background The United States has experienced high levels of excess mortality during the COVID-19 pandemic and also has high prevalence of overweight and obesity, which increases the risk of severe infection and death from the virus. This study uses multiple cause of death data to estimate excess premature cardiovascular disease mortality in the USA in 2020 for which overweight and obesity was a risk factor. Methods The contribution of overweight and obesity to premature (35–74 years) cardiovascular disease mortality was measured as cardiovascular disease reported on the death certificate with one or more of diabetes, chronic kidney disease, obesity, lipidemias or hypertensive heart disease (DKOLH-CVD). Excess mortality was calculated as the difference between actual and expected age-standardised death rates. Expected deaths were estimated using negative binomial regressions of monthly deaths during 2010–19. Results Excess DKOLH-CVD mortality in March-December 2020 was 29% (95% uncertainty interval 28–31%) for males and 30% (28–32%) for females, much higher than for all causes (males 19% (18–21%), females 16% (14–17%)). Excess mortality was higher where two or more DKOLH conditions (males 40% (37–43%), females 41% (37–44%)) or obesity (males 42% (38–45%), females 47% (43–51%)) were reported. One-half of excess DKOLH-CVD mortality was reported as due to COVID-19, lower than the four-fifths of excess all-cause deaths. For home deaths, just over 10% of excess mortality for each cause classification was reported as due to COVID-19. Conclusions Excess premature cardiovascular disease mortality in the USA for which overweight and obesity was a risk factor was considerably higher than for all causes, exacerbating adverse pre-pandemic trends. The contribution of COVID-19 to excess mortality appears significantly under-reported for home deaths.

Exposure to low ambient temperatures has previously been demonstrated to markedly improve glucose homeostasis in both rodents and humans. Although the brown adipose tissue is key in mediating these beneficial effects in rodents, its contribution appears more limited in humans. Hence, the exact tissues and underlying mechanisms that mediate cold-induced improvements in glucose homeostasis in humans remain to be fully established. In this review, we evaluated the response of the main organs involved in glucose metabolism (i.e. pancreas, liver, (white) adipose tissue, and skeletal muscle) to cold exposure and discuss their potential contribution to cold-induced improvements in glucose homeostasis in humans. We here show that cold exposure has widespread effects on metabolic organs involved in glucose regulation. Nevertheless, cold-induced improvements in glucose homeostasis appear primarily mediated via adaptations within the skeletal muscle and (presumably) white adipose tissue. Since the underlying mechanisms remain elusive, future studies should be aimed at pinpointing the exact physiological and molecular mechanisms involved in humans. Nonetheless, cold exposure holds great promise as a novel, additive lifestyle approach to improve glucose homeostasis in insulin resistant individuals. Parts of this graphical abstract were created using (modified) images from Servier Medical Art, licensed under the Creative Commons Attribution 3.0 Unported License. TG = thermogenesis, TAG = triacylglycerol, FFA = free fatty acid, SLN = sarcolipin, UCP3 = uncoupling protein 3, β2-AR = beta-2 adrenergic receptor, SNS = sympathetic nervous system.

Background/Objective As the obesity epidemic continues, the understanding of macronutrient influence on central nervous system function is critical for understanding diet-induced obesity and potential therapeutics, particularly in light of the increased sugar content in processed foods. Previous research showed mixed effects of sucrose feeding on body weight gain but has yet to reveal insight into the impact of sucrose on hypothalamic functioning. Here, we explore the impact of liquid sucrose feeding for 12 weeks on body weight, body composition, caloric intake, and hypothalamic AgRP neuronal function and synaptic plasticity. Methods Patch-clamp electrophysiology of hypothalamic AgRP neurons, metabolic phenotyping and food intake were performed on C57BL/6J mice. Results While mice given sugar-sweetened water do not gain significant weight, they do show subtle differences in body composition and caloric intake. When given sugar-sweetened water, mice show similar alterations to AgRP neuronal excitability as in high-fat diet obese models. Increased sugar consumption also primes mice for increased caloric intake and weight gain when given access to a HFD. Conclusions Our results show that elevated sucrose consumption increased activity of AgRP neurons and altered synaptic excitability. This may contribute to obesity in mice and humans with access to more palatable (HFD) diets.

Background Deoxyguanosine kinase (DGUOK) deficiency is one of the genetic causes of mitochondrial DNA depletion syndrome (MDDS) in humans, leading to the hepatocerebral or the isolated hepatic form of MDDS. Mouse models are helpful tools for the improvement of understanding of the pathophysiology of diseases and offer the opportunity to examine new therapeutic options. Methods Herein, we describe the generation and metabolic characterization of a mouse line carrying a homozygous Dguok F180S/F180S mutation derived from an N -ethyl- N -nitrosourea-mutagenesis screen. Energy expenditure (EE), oxygen consumption (VO 2 ) and carbon dioxide production (VCO 2 ) were assessed in metabolic cages. LC-MS/MS was used to quantify plasma adrenal steroids. Plasma insulin and leptin levels were quantified with commercially available assay kits. Results Mutant animals displayed significantly lower body weights and reduced inguinal fat pad mass, in comparison to unaffected littermates. Biochemically, they were characterized by significantly lower blood glucose levels, accompanied by significantly lower insulin, total cholesterol, high density lipoprotein and triglyceride levels. They also displayed an almost 2-fold increase in transaminases. Moreover, absolute EE was comparable in mutant and control mice, but EE in mutants was uncoupled from their body weights. Histological examination of inguinal white adipose tissue (WAT) revealed adipocytes with multilocular fat droplets reminiscent of WAT browning. In addition, mRNA and protein expression of Ucp1 was increased. Mutant mice also presented differing mitochondrial DNA content in various tissues and altered metabolic activity in mitochondria, but no further phenotypical or behavioral abnormalities. Preliminary data imply normal survival of Dguok F180S/F180S mutant animals. Conclusion Taken together, DGUOK mutation F180S leads to a lean phenotype, with lower glucose, insulin, and lipid levels rendering this mouse model not only useful for the study of MDDS forms but also for deciphering mechanisms resulting in a lean phenotype.

The purpose of this study was to determine the association between changes in physical activity and changes in body weight in a cluster-randomized weight loss trial conducted in an underserved population in Louisiana. This study reports analyses conducted in the intervention group only, which was a 24-month multi-component weight loss program delivered by health coaches embedded in primary care clinics. Physical activity was assessed at baseline and at 6, 12, and 24 months of follow-up and changes in body weight were expressed as percent weight change from baseline. Among the sample of 402 patients, percent changes in body weight (mean ± SE) across increasing tertiles of changes in walking between baseline and 24 months were −3.2 ± 1.0%, −5.5 ± 0.9%, and −7.3 ± 0.9%, respectively (p = 0.001). Changes in body weight across increasing tertiles of changes in moderate-to-vigorous-intensity activity between baseline and 24 months were −4.3 ± 1.0%, −5.0 ± 0.9%, and −7.0 ± 0.9%, respectively (p = 0.04). In conclusion, this multi-component intervention resulted in clinically significant weight loss, and greater increases in physical activity over the intervention period were associated with greater percent reductions in body weight. These results are consistent with those from other studies conducted primarily in non-underserved populations.

Objective Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. Methods Cohort study of 346,586 persons born during 1930–1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18–49 and from age 50. Results During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98–1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11–1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85–1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34–1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83–0.99) per 500 g higher birthweight]. Conclusion BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight.

Objective To estimate usual dietary intake (UDI), physical activity (PA), and their association with weight loss and body composition in patients who underwent Roux-en-Y gastric bypass (RYGB) after five years in the Federal District, Brazil. Methods We assessed anthropometry and body composition using bioimpedance, and dietary intake and PA with three nonconsecutive 24-h recalls. PC-Side was used to estimate UDI. Dietary patterns (DPs) were identified through principal component analysis, and association between UDI and PA with percentage of total weight loss (%TWL) and fat-free mass (FFM) through multinomial logistic regression. Results Sample (n = 124) presented mean (SD) age of 48.9 (9.4) years, median (IQR) of 9 years (7–10) post RYGB, current BMI = 32.3 kg/m² (28.8–35.7), %TWL = 24.7% (10.9), and FFM = 45.1 kg (41.1–51.9). Mean usual energy intake of 1556 kcal/d, with adequate protein intake, poor fiber intake, and excessive carbohydrate, total fat, and added sugar intake, compared to dietary guidelines. Calcium, vitamins C, D, and E presented the greatest inadequacy (15%, 24%, 32%, and 49% of individuals, respectively, reported usual intake below EAR); 83 participants were considered active/very active, according PA. DP with high energy, protein, total fat, saturated fat, and sodium intake, was negatively associated with %TWL (OR = 0.545, p = 0.037). Protein intake was positively associated with FFM (OR = 1.091, p = 0.004). PA was not associated with %TWL or FFM. Conclusion Participants demonstrated intake of carbohydrate, fat, fiber, added sugar not in accordance with guidelines. A DP rich in energy, protein, total fat, saturated fat, and sodium appears to decrease TWL. However, protein intake appears to increase FFM.

Background People with obesity are at increased risk of chronic stress, and this may have been exacerbated during the COVID-19 pandemic. Adverse childhood experiences (ACE) are also associated with both obesity and stress, and may modify risk of stress among people with obesity. The objectives of this study were to evaluate the associations between obesity, ACEs, and stress during the pandemic, and to determine if the association between obesity and stress was modified by ACEs. Methods A longitudinal study was conducted among adults aged 50–96 years ( n = 23,972) from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Study. Obesity and ACEs were collected pre-pandemic (2015–2018), and stress was measured at COVID-19 Exit Survey (Sept-Dec 2020). We used logistic, Poisson, and negative binomial regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the associations between obesity, ACEs, and stress outcomes during the pandemic. Interaction by ACEs was evaluated on the additive and multiplicative scales. Results People with obesity were more likely to experience an increase in overall stressors (class III obesity vs. healthy weight RR = 1.19; 95% CI: 1.12–1.27) as well as increased health related stressors (class III obesity vs. healthy weight RR: 1.25; 95% CI: 1.12–1.39) but did not perceive the consequences of the pandemic as negative. ACEs were also associated an increase in overall stressors (4–8 ACEs vs. none RR = 1.38; 95% CI: 1.33–1.44) and being more likely to perceive the pandemic as negative (4–8 ACEs vs. none RR = 1.32; 95% CI: 1.19–1.47). The association between obesity and stress was not modified by ACEs. Conclusions Increased stress during the first year of the COVID-19 pandemic was observed among people with obesity or ACEs. The long-term outcomes of stress during the pandemic need to be determined.

Background The main purpose of the study is to assess the association between obstructive sleep apnea (OSA) and insulin secretion in children with obesity. Methods We enrolled children and adolescents who attended our pediatric clinic because of obesity and OSA. Glucose homeostasis was assessed through standard 2-h oral glucose tolerance test (OGTT). Nocturnal cardio-respiratory polygraphy was performed for OSA diagnosis. Twenty-two patients underwent a 3-h OGTT to investigate insulin secretion and sensitivity through the oral-minimal model. Results seventy-seven children and adolescents were included in the study. Based on OSA severity, the cohort was divided into three groups (29 mild, 29 moderate, and 19 severe OSA). The group with mild OSA showed lower levels of 30-min glucose (p = 0.01) and 60-min glucose (p = 0.03), and lower prevalence of elevated 1-h glucose (10.4% versus 44.8% in moderate and 31.6% in severe OSA, p = 0.01). The odds for elevated 1-h plasma glucose was 6.2-fold (95%CI 1.6–23.4) higher in subjects with moderate and severe OSA compared to mild OSA (p = 0.007) independent of confounders. Spearman correlation test revealed a positive correlation between 30-min plasma glucose and apnea-hypopnea index (AHI, r = 0.31, p = 0.01), oxygen desaturation index (ODI, r = 0.31, p = 0.009), and mean desaturation (r = 0.25, p = 0.04). The 3-h OGTT study included 22 participants (7 mild, 9 moderate, and 6 severe OSA). The group with mild OSA showed a higher dynamic, static, and total insulin secretion compared to those with moderate and severe OSA (p < 0.0001, p = 0.007, p = 0.007, respectively). AHI was significantly correlated to dynamic insulin secretion (r = −0.48, p = 0.02). Conclusions OSA might impair beta-cell function reducing the pool of promptly releasable insulin in children and adolescents with obesity, in the absence of an effect on insulin sensitivity.

Background Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and metabolic and bariatric surgery (MBS) both improve cardiovascular outcomes in patients with severe obesity and type-2 diabetes (T2D). The aim of the present study was to assess the impact of MBS on major cardiovascular adverse events (MACE) in patients with severe obesity and T2D compared to patients with T2D treated with GLP-1 RA. Subjects and methods In this propensity score matched cohort study on nationwide data, patients with T2D and severe obesity who underwent MBS in Sweden from 2007 until 2019 were identified from the Scandinavian Obesity Surgery Registry and matched to a non-surgical group with T2D treated with GLP-1 RA (81.7% liraglutide, 9.0% dulaglutide, 6.0% exenatide, 1.6% lixisenatide and 0.8% semaglutide) from the general population using generalized linear model. Major outcome was MACE (hospitalization for acute coronary syndrome or cerebrovascular event or all-cause death), evaluated with multivariable Cox regression. Results In total 2161 patients (obesity class I (10.2%), class II (40.3%), class III (49.5%)) were matched to 2161 non-surgical patients (mean age 51.1 ± 9.29 vs 51.5 ± 8.92 years, 64.8% vs. 64.4% women, with mean number of diabetes drugs of 2.5 ± 0.89 vs 2.6 ± 0.87, a mean duration of diabetes of 6.0 ± 4.15 vs 6.0 ± 4.51 years with 44.2% vs. 42.8% being treated with insulin at baseline). During the study period, 113 patients (8-year cumulative incidence 9.3%) compared to 130 non-surgical patients (8-year cumulative incidence 11.3%) suffered from MACE or all-cause mortality (HR 0.76, 95%CI 0.59–0.98), and 69 patients (8-year cumulative incidence 5.1%) compared to 92 non-surgical patients (8-year cumulative incidence 7.6%) suffered from a non-fatal MACE (HR 0.68, 95%CI 0.49–0.93). Conclusion In this matched cohort study, MBS was associated with lower risk for MACE compared to treatment with early GLP-1 RA in patients with T2D.

Background Given inconsistent results in the literature, our objective was to examine the role of early parental feeding practices in children’s growth. Methods Analyses were based on 1245 children from the EDEN mother–child cohort. Parental feeding practices were assessed at the 2-year follow-up by using the Comprehensive Feeding Practices Questionnaire. International Obesity Task Force BMI z-scores were derived from weight and height assessed at 2, 4, 6, and 8 years. Associations between parental feeding practices and child BMI z-scores at 4, 6 and 8 years were assessed by multivariable linear regressions, notably adjusted for 2-year BMI z-score. Analyses were stratified by child sex when relevant. Moreover, interaction and mediation analyses were respectively performed to assess whether parental feeding practices could moderate or mediate the associations between early and later growth. Results For a given BMI z-score at 2 years, parental restriction for weight at 2 years was positively associated with child BMI z-scores from 4 to 8 years (at 8 years: β [95% CI] = 0.09 [0.01; 0.16]). Among boys only, high use of food as a reward was positively associated with later BMI z-scores (at 8 years: β [95% CI] = 0.15 [0.03; 0.27]). Parental feeding practices were not moderating factors in the associations between early and later growth. Parental restriction for weight was a mediating factor in the associations between 2-year BMI z-score and BMI z-scores up to 8 years (mediation: 2.69% [0.27%; 5.11%] of the total effect at 8 years). Conclusions Restriction for weight reasons, often used by parents in response to the child’s high appetite in infancy, appears to lie on the pathway between early and later BMI, but not restriction for health, suggesting that parental way of restricting the child’s food intake matters.

Background Anthropometric measures show high heritability, and genetic correlations have been found between obesity-related traits. However, we lack a comprehensive analysis of the genetic background of human body morphology using detailed anthropometric measures. Methods Height, weight, 7 skinfold thicknesses, 7 body circumferences and 4 body diameters (skeletal breaths) were measured in 214 pairs of twin children aged 3–18 years (87 monozygotic pairs) in the Autonomous Region of Madeira, Portugal. Factor analysis (Varimax rotation) was used to analyze the underlying structure of body physique. Genetic twin modeling was used to estimate genetic and environmental contributions to the variation and co-variation of the anthropometric traits. Results Together, two factors explained 80% of the variation of all 22 anthropometric traits in boys and 73% in girls. Obesity measures (body mass index, skinfold thickness measures, as well as waist and hip circumferences) and limb circumferences loaded most strongly on the first factor, whereas height and body diameters loaded especially on the second factor. These factors as well as all anthropometric measures showed high heritability (80% or more for most of the traits), whereas the rest of the variation was explained by environmental factors not shared by co-twins. Obesity measures showed high genetic correlations (0.75–0.98). Height showed the highest genetic correlations with body diameter measures (0.58–0.76). Correlations between environmental factors not shared by co-twins were weaker than the genetic correlations but still substantial. The correlation patterns were roughly similar in boys and girls. Conclusions Our results show high genetic correlations underlying the human body physique, suggesting that there are sets of genes widely affecting anthropometric traits. Better knowledge of these genetic variants can help to understand the development of obesity and other features of the human physique.

Introduction Obesity is associated with a higher risk of cardiac arrhythmias. Sleeve gastrectomy (SG) is a common bariatric surgery with beneficial effects on weight loss and comorbidities. The study aimed to investigate the prevalence of arrhythmias during maximal exercise testing in patients with moderate-severe obesity and to evaluate the impact of SG on these arrhythmic events. Methods All patients with moderate or severe obesity who were considered suitable candidates for SG between June 2015 and September 2020 were recruited. Each patient underwent three incremental, maximal, ECG-monitored cardiopulmonary exercise test 1 month before and 6 and 12 months after SG; the frequency and complexity of ventricular premature beats (VPBs) and atrial premature beats (APBs) have been evaluated during rest, exercise and recovery phases. Results Fifty patients with severe obesity (BMI 46.39 ± 7.89 kg/m²) were included in the study. After SG, patients presented a decreased BMI (34.15 ± 6.25 kg/m² at 6 months post-SG and 31.87 ± 5.99 kg/m² at 12 months post-SG). At 6 months post-SG, an increase in VPBs, mainly during the recovery phase, was observed. At 12 months post-SG, a reduction in VPBs compared with the 6 months evaluation was showed. Conclusion Although in the early post-surgical phase the risk of exercise-induced arrhythmias may be higher, SG does not seem to increase the occurrence of arrhythmias in the long-term. No life-threating arrhythmias were found during post-SG evaluations.

Background Obesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks. Methods Thirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). Results Exercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses). Conclusion Exercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake. Trial registration Clinicaltrial.gov: NCT02441361.

Background: Sleep problems are known to compound the negative effects of other health issues, such as eating disorders and the associated behavior of binge eating. Previous studies suggested associations between binge eating and sleep problems, but the strength of the relationship is unknown. Methods: We conducted a systematic review with meta-analyses examining the relationship between binge eating and sleep parameters. We searched for studies in Scopus, PubMed, and PsycInfo. The quality of evidence, including risk of bias, was assessed with adaptations of the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies, depending on study design. Data was synthesized as the difference in sleep between people who did or did not have binge eating. Results: Thirty-one reports of studies met our eligibility criteria. Results are presented in 12 meta-analyses. In the 7 reports of studies (with 4448 participants) that assessed poor overall sleep quality, we found poorer overall sleep quality in people with binge eating compared to people without binge eating, with a standardized mean difference of 0.77 (95% confidence interval [CI] 0.61-0.92; P < 0.001), which is a large effect size. In addition, we found evidence that people with binge eating had significantly greater hypersomnia/daytime sleepiness (7 reports of studies with 4370 participants), insomnia (5 reports of studies with 12,733 participants), and difficulty falling asleep (3 reports of studies with 4089 participants) compared to people without binge eating, with moderate effect sizes (standardized mean differences of 0.57-0.66). Conclusions: People with binge eating exhibit poorer overall sleep quality compared to people without binge eating, and may also exhibit greater hypersomnia/daytime sleepiness, insomnia, and difficulty falling asleep. It is recommended that healthcare professionals routinely screen for poor overall sleep quality when treating people with binge eating-and address sleep difficulties when present.

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Background/objectives This cross-sectional study examined the relationship between the oxygen (O2) cost of walking and body composition metrics, while considering potential covariates such as disability status, step length, and cadence, in persons with multiple sclerosis (MS). Subjects/methods The sample included 63 persons with MS across a wide distribution of body mass index (BMI). O2 cost of walking was assessed using portable, indirect calorimetry, and percent body fat (%Fat), fat-free mass (FFM), bone mineral content, bone mineral density (BMD), and weight/FFM were determined from dual-energy x-ray absorptiometry. Other outcome measures included step length, cadence, physical activity, and disability status. Results The O2 cost of walking had small-to-moderate associations with BMI (rs = –31, p = 0.015), %Fat (rs = –0.26, p = 0.041), and BMD (rs = –0.31, p = 0.013). O2 cost of walking was significantly associated with these outcomes even after controlling for age, sex, disability status, and gait outcomes. The O2 cost of walking was further significantly associated with shorter step length (rs = –0.40, p = 0.001), slower cadence (rs = –0.38, p = 0.002), and higher disability status (rs = 0.44, p < 0.001), but not physical activity. Body composition metrics were not associated with gait parameters, physical activity or disability status in our sample of persons with mild-to-moderate MS. Conclusions The results indicated that higher O2 cost of walking was associated with lower fat and worse bone health after taking factors such as disability status into consideration. Researchers may focus on interventions that change body composition, or perhaps gait profiles, as possible approaches for changing O2 cost of walking and its consequences such as disability status in persons with MS.

Background Obesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma adipokines and COVID-19 severity, systemic inflammation, clinical parameters, and outcome of COVID-19 patients. Methods In this multi-centre prospective cross-sectional study, we collected blood samples and clinical data from COVID-19 patients. The severity of COVID-19 was classified as mild (no hospital admission), severe (ward admission), and critical (ICU admission). ICU non-COVID-19 patients were also included and plasma from healthy age, sex, and BMI-matched individuals obtained from Lifelines. Multi-analyte profiling of plasma adipokines (Leptin, Adiponectin, Resistin, Visfatin) and inflammatory markers (IL-6, TNFα, IL-10) were determined using Luminex multiplex assays. Results Between March and December 2020, 260 SARS-CoV-2 infected individuals (age: 65 [56–74] BMI 27.0 [24.4–30.6]) were included: 30 mild, 159 severe, and 71 critical patients. Circulating leptin levels were reduced in critically ill patients with a high BMI yet this decrease was absent in patients that were administered dexamethasone. Visfatin levels were higher in critical COVID-19 patients compared to non-COVID-ICU, mild and severe patients (4.7 vs 3.4, 3.0, and 3.72 ng/mL respectively, p < 0.05). Lower Adiponectin levels, but higher Resistin levels were found in severe and critical patients, compared to those that did not require hospitalization (3.65, 2.7 vs 7.9 µg/mL, p < 0.001, and 18.2, 22.0 vs 11.0 ng/mL p < 0.001). Conclusion Circulating adipokine levels are associated with COVID-19 hospitalization, i.e., the need for oxygen support (general ward), or the need for mechanical ventilation and other organ support in the ICU, but not mortality.

Objective To estimate the risk of cardiovascular disease (CVD) in older adults with overweight or obesity without metabolic risk factors using a Bayesian survival analysis. Design Prospective cohort study with median follow-up of 9.7 years. Setting Newcastle, New South Wales, Australia. Participants A total of 2313 community-dwelling older men and women. Intervention/exposure Participants without known CVD and with a body mass index (BMI) ≥ 18.5 kg m² were stratified by BMI and metabolic risk to create six BMI-metabolic health categories. Metabolic risk was defined according to the International Diabetes Federation criteria for metabolic syndrome. ‘Metabolically healthy’ was defined as absence of metabolic risk factors. Bayesian survival analysis, incorporating prior information from a previously published meta-analysis was used to assess the effect of BMI-metabolic health categories on time from recruitment to CVD. Main outcome Incident physician-diagnosed CVD, defined as fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, angina, or coronary revascularisation procedure, was determined by linkage to hospital admissions records and Medicare Australia data. Secondary outcomes were cardiovascular mortality and all-cause mortality. Results From 2313 adults with complete metabolic health data over a median follow-up of 9.7 years, 283 incident CVD events, 58 CVD related deaths and 277 deaths from any cause occurred. In an adjusted Bayesian survival model of complete cases with informative prior and metabolically healthy normal weight as the reference group, the risk of CVD was increased in metabolically healthy overweight (HR = 1.52, 95% credible interval 0.96–2.36), and in metabolically healthy obesity (HR = 1.86, 95% credible interval 1.14–3.08). Imputation of missing metabolic health and confounding data did not change the results. Conclusion There was increased risk of CVD in older adults with overweight or obesity, even in the absence of any metabolic abnormality. This argues against the notion of ‘metabolically healthy’ overweight or obesity.

Background/objectives Obesity, defined as excessive fat accumulation that represents a health risk, is increasing in adults and children, reaching global epidemic proportions. Body mass index (BMI) correlates with body fat and future health risk, yet differs in prediction by fat distribution, across populations and by age. Nonetheless, few genetic studies of BMI have been conducted in ancestrally diverse populations. Gene expression association with BMI was assessed in the Multi-Ethnic Study of Atherosclerosis (MESA) in four self-identified race and ethnicity (SIRE) groups to identify genes associated with obesity. Subjects/methods RNA-sequencing was performed on 1096 MESA participants (37.8% white, 24.3% Hispanic, 28.4% African American, and 9.5% Chinese American) and linear models were used to assess the association of expression from each gene for its effect on BMI, adjusting for age, sex, sequencing center, study site, five expression and four genetic principal components in each self-identified race group. Sample-size-weighted meta-analysis was performed to identify genes with BMI-associated expression across ancestry groups. Results Within individual SIRE groups, there were zero to three genes whose expression is significantly (p < 1.97 × 10–6) associated with BMI. Across all groups, 45 genes were identified by meta-analysis whose expression was significantly associated with BMI, explaining 29.7% of BMI variation. The 45 genes are expressed in a variety of tissues and cell types and are enriched for obesity-related processes including erythrocyte function, oxygen binding and transport, and JAK-STAT signaling. Conclusions We have identified genes whose expression is significantly associated with obesity in a multi-ethnic cohort. We have identified novel genes associated with BMI as well as confirmed previously identified genes from earlier genetic analyses. These novel genes and their biological pathways represent new targets for understanding the biology of obesity as well as new therapeutic intervention to reduce obesity and improve global public health.