Healthy Weight Individuals Research Articles

Relationship between metabolically healthy overweight/obesity and risk of type 2 diabetes in different ethnicity: a prospective cohort study in southwest China

BackgroundTo estimate and compare the association between metabolically healthy overweight/obesity (MHO) and the risk of type 2 diabetes (T2DM) among different ethnic groups in southwest China, while also exploring possible ethnic differences.MethodsThis is a prospective cohort study of 6,820 participants in Southwest China. MHO was defined as body mass index (BMI) ≥ 24 kg/m2 and the presence of ≤ 1 component of metabolic syndrome. Cox proportional risk models were utilized to analyze the association between MHO and the risk of T2DM.ResultsThe median follow-up time was 6.58 years, during which 708 new cases of T2DM were diagnosed. In the total population, after adjusting for confounding factors, MHO was found to increase the risk of T2DM compared to metabolically healthy normal weight (MHNW) individuals (HR = 1.49, 95% CI: 1.15–1.93). Subgroup analysis by ethnicity revealed that, MHO increased the risk of T2DM in the Han population (HR = 1.64, 95% CI: 1.21–2.23), however, the difference was not statistically significant in the ethnic minority population.The results of sensitivity analysis further supported the robustness of these findings. Meanwhile, stratified by sex, age, and urban/rural, it was found that ethnic differences in the association between MHO and T2DM still existed, however, it is important to note that the association between MHO and T2DM was not statistically significant in the Han population subgroup aged ≥ 45 years (p > 0.05).ConclusionMHO was associated with an increased risk of T2DM compared to MHNW, and there are ethnic differences. Future interventions need to be strengthened for Han Chinese key populations to reduce the risk of T2DM.

An Examination of Exercise Intensity and its Impact on the Acute Release of Irisin Across Obesity Status: A Randomized Controlled Crossover Trial.

Limited data exist regarding the impact of exercise intensity on irisin release and its association with insulin sensitivity in individuals of differing obesity status. The objective of this study was to investigate the impact of exercise intensity on the acute release of irisin in healthy weight individuals and individuals with obesity, and whether irisin release during acute exercise was associated with greater insulin sensitivity across obesity status. A randomized controlled crossover study was conducted on 26 non-obese (NOB) (BMI: 22.2±1.5 kg/m2) and 26 OB (BMI: 33.9±6.5 kg/m2) adults who performed an acute bout of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and rest. Irisin was quantified via ELISA and western blotting, and insulin sensitivity (Si) was estimated using the Matsuda index. OB displayed a significantly lower level of circulating irisin and protein expression compared to NOB (p<0.01). Insulin sensitivity was positively correlated with irisin release during MICT and HIIT in NOB (all p<0.05), but not in OB. Regarding irisin expression, NOB with high-Si had a 2.03-fold (p<0.05) increase during HIIT, while OB with high-Si had only a 1.54-fold increase (p<0.05). These results suggest that irisin is released differently according to obesity status and varying exercise intensities. OB individuals have a blunted irisin response to acute exercise and lower baseline irisin concentrations compared to NOB individuals. Although exercise stimulates irisin release in NOB individuals, only a greater exercise intensity stimulates irisin release in OB individuals. These findings are clinically relevant, as irisin is associated with greater insulin sensitivity.

A Bayesian network analysis of the probabilistic relationships between metabolically healthy obesity and cardiovascular disease risk under new diagnostic criteria.

The relationship between metabolically healthy obesity (MHO) and cardiovascular disease (CVD) risk remains debated. The critical point may be the lack of consensus on MHO's definition and diagnostic criteria. This study aimed to investigate the association of MHO status with arteriosclerosis-CVD (ASCVD) risk in Chinese under new diagnostic criteria. Participants aged 35-79 in the 2009 China Health and Nutrition Survey cohort were included. The 10-year ASCVD risk was predicted by the prediction for ASCVD risk in China, and participants with a predicted risk of ⩾ 10% were classified into the high-risk group. The Bayesian network (BN) models were constructed to characterize the multivariable probabilistic connections between metabolically obesity phenotypes and ASCVD risk. The 10-year ASCVD risk score and the proportion of individuals at ASCVD high risk were significantly different between metabolically obesity phenotypes (P< 0.001). BN reasoning results showed that MHO individuals were not significantly associated with a 10-year ASCVD risk. Among metabolically unhealthy individuals, the conditional probability of high ASCVD risk increased with the Body Mass Index (BMI), with the conditional probability of high ASCVD risk was 24.63% (95% CI: 22.81-26.55%), 32.97% (95% CI: 30.75-35.27%) and 40.2% (95% CI: 36.64-43.86%) for metabolically unhealthy normal weight (MUNW), metabolically healthy overweight weight (MHOW), and metabolically unhealthy obesity (MUO) group, respectively. Subgroup analysis showed that MHO individuals were at increased risk of CVD compared with metabolically healthy normal weight (MHNW) individuals only in females. These results showed that there was no significant increase in ASCVD risk of MHO phenotype based on the new diagnostic criteria, suggesting that MHO is in a relatively healthy state.

A Case-Control Study Supports Genetic Contribution of the PON Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease.

The paraoxonase (PON) gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare PON variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features. Polymorphisms rs705379 and rs854552 in the PON1 gene displayed significant association with MASLD stage and fibrosis, respectively. Additionally, rare PON1 variants were strongly associated with obesity. This study thereby reinforces the genetic foundation of PON1 in obesity and various MASLD-related liver features, by extending previous findings from common variants to include rare variants. Additionally, rare and very rare variants in PON2 were discovered to be associated with MASLD-related hepatic fibrosis. Notably, we are the first to report an association between naturally occurring rare PON2 variants and MASLD-related liver fibrosis. Considering the critical role of liver fibrosis in MASLD outcome, PON2 emerges as a possible candidate for future research endeavors including exploration of biomarker potential.

Metabolic dysfunction associated fatty liver disease in healthy weight individuals

Metabolic dysfunction associated fatty liver disease (MAFLD) is an increasing public health problem, affecting one third of the global population. Contrary to conventional wisdom, MAFLD is not exclusive to obese or overweight individuals. Epidemiological studies have revealed a remarkable prevalence among healthy weight individuals, leading investigations into the genetic, lifestyle, and dietary factors that contribute to the development of MAFLD in this population. This shift in perspective requires reconsideration of preventive strategies, diagnostic criteria and therapeutic approaches tailored to address the unique characteristics of MAFLD healthy weight individuals. It also underscores the importance of widespread awareness and education, within the medical community and among the general population, to promote a more inclusive understanding of liver metabolic disorders. With this review, we aim to provide a comprehensive exploration of MAFLD in healthy weight individuals, encompassing epidemiological, pathophysiological, and clinical aspects.

Decoupling of desire and salivation over repeated chocolate consumption and the moderating role of food legalizing

This study aimed to investigate the responses in desire and salivation during repeated chocolate consumption, and examining how these responses are influenced by a relaxed relationship with food, or 'food legalizing'. Salivation is often used as a proxy for desire, though evidence for this correlation is mixed. We hypothesized that both desire and salivation would decrease with repeated chocolate intake. Additionally, research has suggested that eating styles may affect habituation rates. We proposed that individuals with the food legalizing trait would habituate more rapidly to chocolate, providing an alternative mechanism to reward sensitivity associated with restrained eating. Fifty healthy-weight individuals participated in the study, consuming five blocks of chocolate (each 4 g, 22 calories) over trials. After the trials, participants were allowed to eat as much chocolate as they desired. The results showed that salivation was not correlated with self-reported desire over repeated chocolate consumption. While desire decreased with repeated intake and predicted ad libitum consumption, salivation increased and did not predict ad libitum consumption. Furthermore, food legalizing moderated the rate of responding in terms of the desire to eat but did not affect salivary flow. These findings suggest that salivation is not a reliable physiological measure of desire when eating chocolate. Instead, salivation appears to reflect sensitization to the sensory characteristics of chocolate and is less predictive of subsequent ad libitum chocolate consumption than self-reported desire. Lastly, having a carefree relationship with chocolate may help regulate its consumption, highlighting the potential benefits of a relaxed attitude toward food.

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

BackgroundFundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions.MethodsThe study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty.ResultsPrincipal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues.ConclusionsThe present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations.

Abstract P344: Epidemiology and Burden of Patients Living With Overweight/Obesity and Established Atherosclerotic Cardiovascular Disease

Introduction: Obesity is a serious chronic, progressive metabolic disorder associated with increased morbidity and mortality. Compared with individuals of healthy weight, those living with overweight/obesity are at higher risk for atherosclerotic cardiovascular disease (ASCVD). Given the established relationship between obesity and ASCVD, individuals living with overweight/obesity and ASCVD may gain additional benefits by directly treating obesity. Hypothesis: We assessed the hypothesis that comorbidity burden is higher in adults living with overweight/obesity and ASCVD than in those without ASCVD. Methods: This was a retrospective real-world study using Optum Market Clarity, a linked electronic medical record and administrative health care claims data set. Adults living with overweight and ≥1 weight-related comorbidity or obesity were included. The point prevalence of ASCVD was described for the overall study period (1/1/2017 to 6/30/2021). Stratified prevalence analyses were conducted by age group (ie, ≤45 years, 45-64 years, and ≥65 years). Comorbidity burden was assessed as percentage of patients with weight-related comorbidities. Results: The study encompassed 4,773,152 patients eligible for prescription weight management treatment; 245,824 (5.3%) had been diagnosed with ASCVD. Over the study period of 2017-2021, with a median (Q1-Q3) follow-up time of 43.7 (29.0-57.2) months, peripheral arterial disease was the most prevalent (2.5%) ASCVD condition among these patients, followed by ischemic heart disease (2.2%) and ischemic or hemorrhagic stroke (1.3%). Yearly prevalence of peripheral arterial disease, ischemic heart disease, and ischemic or hemorrhagic stroke within the study period ranged from 2.3%-3.8%, 2.0%-3.2%, and 1.2%-1.8%, respectively. These patients, compared with those without ASCVD, had a mean age of 63.8 vs 49.4 years and mean BMI of 33.4 vs 34.7 kg/m 2 , and 52.7% vs 40.8% were male (all P &lt;.001). The prevalence of ASCVD increased with age: patients aged ≥65 years had an overall prevalence of 14.1%, with yearly prevalence ranging from 13.3%-18.8%, compared with 5.5% in patients aged 45 to 64 years, with yearly prevalence ranging from 5.2%-7.8%. Overall, patients with ASCVD had a higher comorbidity burden than patients without ASCVD, including type 2 diabetes (49.7% vs 17.6%), prediabetes (15.5% vs 9.0%), dyslipidemia (75.6% vs 30.4%), obstructive sleep apnea (22.3% vs 10.2%), and chronic kidney disease (21.1% vs 3.7%; all P &lt;.001). Conclusions: ASCVD is prevalent among people living with overweight/obesity, to a greater extent in older and male individuals. People living with ASCVD and overweight/obesity bear a substantially higher comorbidity burden compared with those without ASCVD. Further evidence is needed to support pharmacotherapy-based chronic weight management to lower the cardiovascular disease burden in this population.

Patient satisfaction and patient-reported outcomes do not vary by BMI class in total hip arthroplasty.

Obesity has been identified as a risk factor for postoperative complications in patients undergoing total hip arthroplasty (THA). This study aimed to investigate patient-reported outcomes, pain, and satisfaction as a function of body mass index (BMI) class in patients undergoing THA. 1736 patients within a prospective observational study were categorized into BMI classes. Pre- and postoperative Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR), satisfaction, and pain scores were compared by BMI class using one-way ANOVA. Healthy weight patients reported the highest preoperative HOOS JR (56.66 ± 13.35) compared to 45.51 ± 14.45 in Class III subjects. Healthy weight and Class III patients reported the lowest (5.65 ± 2.01) and highest (7.06 ± 1.98, p < 0.0001) preoperative pain, respectively. Changes in HOOS JR scores from baseline suggest larger improvements with increasing BMI class, where Class III patients reported an increase of 33.7 ± 15.6 points at 90days compared to 26.1 ± 17.1 in healthy weight individuals (p = 0.002). Fewer healthy weight patients achieved the minimal clinically important difference (87.4%) for HOOS JR compared to Class II (96.5%) and III (94.7%) obesity groups at 90days postoperatively. Changes in satisfaction and pain scores were largest in the Class III patients. Overall, no functional outcomes varied by BMI class postoperatively. Patients of higher BMI class reported greater improvements following THA. While risk/benefit shared decision-making remains a personalized requirement of THA, this study highlights that utilization of BMI cutoff may not be warranted based on pain and functional improvement.

Obesity is Associated with Increased Risk of New-Onset Chronic Rhinosinusitis: A United States Population-Based Cohort Study.

The aim of this study was to determine the risk of a new-encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large-population-based analytics platform. Retrospective cohort analysis SETTING: The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study. After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new-encounter diagnosis of unspecified CRS and CRSwNP compared to healthy-weight individuals. The obesity cohort had the greatest increased risk of new-onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20-1.25) and 1.26 (95% CI: 1.24-1.28) 1 and 2 years following BMI classification, respectively. Our study indicates an association between obesity and new-onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity-associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.

The obesity paradox exists in Asia: A systematic review and meta-analysis of body mass index effects on clinical outcomes following percutaneous coronary intervention in Asia.

Cardiovascular diseases (CVDs) are major contributors to illness and death globally. Body mass index (BMI) is a well-established prognostic factor on cardiovascular risk outcome. Numerous investigations have provided evidence for the existence of the obesity paradox after percutaneous coronary intervention (PCI). However, the association between BMI and the results following PCI has not been extensively investigated in Asian populations. The research aims to fill the current void in understanding by investigating the association between BMI and clinical consequences following PCI, with a particular focus on Asian individuals. A systematic search was conducted through PubMed, ScienceDirect, and Cochrane Library to identify studies examining the effect of BMI on clinical outcome after PCI in Asia. R Studio 4.3.2 software was used to carry out the analysis of the data. A total of 182,110 patients who had gone through PCI were found in the 5 included cohorts. A meta-analysis conducted on the subjects revealed that patients who were overweight (odds ratio [OR] = 0.60, 95% confidence interval [CI] [0.57, 0.63], P < 0.0001) had a lower risk of all-cause mortality compared to individuals with a healthy weight and patients with obesity (OR = 0.65, 95% CI [0.41, 1.05], P = 0.006) had a lower risk of all-cause mortality than healthy weight individuals. The study also found that overweight patients (OR = 0.60, 95% CI [0.39, 0.91], P = 0.02) had a lower risk of cardiac mortality. In addition, obese patients (OR = 0.41, 95% CI [0.19, 0.88], P = 0.02) had a lower risk of noncardiac mortality. However, the study found that there were no differences in major adverse cardiovascular event, myocardial infarction, and bleeding between all patient groups. This meta-analysis supports the presence of an obesity paradox after PCI in Asian populations. The obesity paradox was evident in all-cause mortality, cardiac mortality, and noncardiac mortality.

Abstract TMP100: Acute Ischemic Stroke in Young Adults: A Comparative Analysis of Outcomes and Mortality in Metabolically Healthy Obese vs. Normal Weight Individuals, 2016-2019 Cohort

Introduction: Rising obesity rates and the increasing prevalence of stroke in the metabolically healthy obese (MHO) necessitate examining its association in younger (18-44 year) populations. Analyzing acute ischemic stroke (AIS) trends and outcomes in MHO vs. metabolically healthy normal weight (MH-NW). Methods: Data from the National Inpatient Sample (2016-2019) was analyzed to identify young MHO and MH-NW AIS patients using ICD-10 codes. Demographics, trends, and outcomes were compared using multivariable statistical approaches. Results: Of 26,949,310 young metabolically healthy individuals studied between 2016 and 2019, 47,795 had AIS, 4,985 were MHO, and 42,810 were MH-NW. The median AIS patient age was 35. The MHO cohort was primarily female, white, in the lowest income quartile, with private insurance. Most were hospitalized in southern US urban teaching hospitals. Notably, the MHO cohort had higher rates of specific comorbidities like depression, chronic pulmonary disease, and obstructive sleep apnea but lower rates of drug abuse and peripheral vascular disease. The in-hospital mortality rate was significantly lower in MHO patients (6.0% vs. 8.6%). Hospitalization length and cost did not significantly differ between groups. From 2016 to 2019, AIS incidence rose slightly, significant only for the MH-NW cohort. Adjusted multivariable odds ratios revealed no significant difference in AIS occurrence between MHO and MH-NW overall (aOR: 1.02, p=0.701), in males (aOR: 0.88, p=0.161) or females (aOR: 1.06, p=0.363). However, MHO-associated AIS had lower odds of in-hospital mortality than MH-NW (aOR: 0.60, p=0.021). Conclusion: AIS incidence was consistent across young metabolically healthy groups regardless of obesity status. However, we noted a paradoxical 40% reduction in in-hospital mortality in the MHO cohort. This underscores the complex MHO-stroke relationship in young adults, signaling a need for in-depth research and tailored interventions.

Assessment of an IMU-Based Experimental Set-Up for Upper Limb Motion in Obese Subjects.

In recent years, wearable systems based on inertial sensors opened new perspectives for functional motor assessment with respect to the gold standard motion capture systems. The aim of this study was to validate an experimental set-up based on 17 body-worn inertial sensors (Awinda, Xsens, The Netherlands), addressing specific body segments with respect to the state-of-the art system (VICON, Oxford Metrics Ltd., Oxford, UK) to assess upper limb kinematics in obese, with respect to healthy subjects. Twenty-three obese and thirty healthy weight individuals were simultaneously acquainted with the two systems across a set of three tasks for upper limbs (i.e., frontal arm rise, lateral arm rise, and reaching). Root Mean Square error (RMSE) was computed to quantify the differences between the measurements provided by the systems in terms of range of motion (ROM), whilst their agreement was assessed via Pearson's correlation coefficient (PCC) and Bland-Altman (BA) plots. In addition, the signal waveforms were compared via one-dimensional statistical parametrical mapping (SPM) based on a paired t-test and a two-way ANOVA was applied on ROMs. The overall results partially confirmed the correlation and the agreement between the two systems, reporting only a moderate correlation for shoulder principal rotation angle in each task (r~0.40) and for elbow/flexion extension in obese subjects (r = 0.66), whilst no correlation was found for most non-principal rotation angles (r < 0.40). Across the performed tasks, an average RMSE of 34° and 26° was reported in obese and healthy controls, respectively. At the current state, the presence of bias limits the applicability of the inertial-based system in clinics; further research is intended in this context.

An Important Problem in AdV-36 Seropositive Obesity Patients: Leptin Resistance

Adenoviruses are naked viruses with an icosahedral nucleocapsid containing a 36 kb linear double-stranded DNA genome that encodes 30-40 proteins. The word "obesity" in Latin means "because of feeding". Obesity is an energy metabolism pathology that paves the way for physical and psychological problems with excessive fat accumulation that can impair health. Body mass index (BMI), unaffected by gender and age, is the most useful indicator of overweight and obesity at the population level. The concept of infectobesity was first introduced in 1978 after the data showed that viruses might also play a role in obesity cases. In the same year, adenovirus 36 (AdV-36) was isolated from the stool of a six-year-old girl with diabetes who was admitted to the hospital with the complaint of enteritis. One of the adipokines important for obesity is leptin. Leptin regulates food intake and energy metabolism by having a "negative feedback" effect on the hypothalamus. Leptin acts as a sensor that acutely regulates energy metabolism by creating hunger and satiety signals and it also regulates the amount of body fat and the required weight of the person by adjusting its concentration in the plasma according to the nutritional status. Changes in body weight and metabolic status are often associated with acute or chronic inflammatory processes. Human cells infected by AdV-36 showed greater differentiation and higher lipid accumulation than uninfected control cells, which increases the prevalence of obesity. There are two fractions of serum leptin, protein-bound and free form. The balance between these two fractions depends on serum leptin and soluble leptin receptor (sLR) plasma concentration, which is adversely affected by BMI. AdV-36 infection reduces norepinephrine and leptin levels. These two effects contribute to obesity by increasing appetite and food intake. In this study, it was aimed to determine the presence of immunoglobulin G against AdV-36 in the blood serum of obesity patients (BMI≥ 30) and healthy weight individuals (18.5≤ BMI≤ 25), and also aimed to determine and compare the leptin and soluble leptin receptor levels of these individuals. In this study, 10 ml of blood was collected on an empty stomach from obese individuals (n= 101; BMI≥ 30) and healthy individuals (n= 96; 18.5≤ BMI≤ 25) between the ages of 18-55. All participants consisted of who were not taking any medication and were not immunosuppressed. Blood samples separated into their serum were analyzed for AdV-36 IgG, leptin, and soluble leptin receptor levels. Mean, standard deviation, and percentage values were calculated by descriptive statistical analysis. The data with normal distribution were evaluated with the paired and independent sample t-test and data with abnormal distribution were evaluated with the paired and independent sample Mann-Whitney U test. Findings with a p-value less than 0.05 were considered statistically significant. In conclusion, leptin levels in obese individuals who were not infected with Adv-36 were found to be low, in line with the principle that "insufficient leptin synthesis has a role in the pathophysiology of obesity". When AdV-36 infection is added to the obesity picture, it may be due to the fact that it increases leptin synthesis in patients and the level of soluble leptin receptors increases in response to the increased leptin level, that AdV-36 suppresses the binding of the leptin molecule to its receptor, which leads to leptin resistance.

Inflammatory and intestinal permeability biomarkers in healthy participants on long term vegan, vegetarian, omnivore and low-carbohydrate high-fat diet

Vegan, vegetarian and low-carbohydrate high fat (LCHF) diets can all offer several health benefits, if food choices are appropriate. In most studies examining their effects on systemic inflammation, participants were either overweight, on a weight loss programme or not matched for BMI, or had a pre-existing condition such as type 2 diabetes mellitus or hypertension. Little is known about the effects of dietary patterns on healthy and normal weight individuals. The aim of the present study was therefore to assess and directly compare inflammatory and intestinal permeability status in healthy participants following aforementioned or omnivore diet for at least 6 months. In this cross-sectional study, we measured the inflammatory biomarkers IL-6, TNF-α and CRP, and the markers of intestinal permeability LBP and zonulin, along with the analysis of lifestyle aspects, dietary intakes and physical activity, in 89 healthy participants. The groups were matched for sex, age and BMI. There were no differences in any of the measured parameters between the four groups and we found no strong correlations with dietary intakes. Using cluster analysis, participants were divided into eight clusters with more or less favourable inflammatory profiles; all clusters contained representatives of all patterns and all patterns were represented in each cluster. Significant differences between clusters were in the intake of mono-unsaturated fatty acids, ω-3/ω-6 ratio, phase angle and working two shifts. In healthy, normal-weight individuals, inflammatory status therefore does not depend on the dietary pattern itself, but is rather more complexly regulated and associated with dietary and non-dietary factors.

Modified High-Intensity Interval Training and its effects on immunometabolic regulation in sedentary young adults with overweight and obesity.

Sedentary lifestyles can contribute to obesity and other diseas-es; while chronic low-grade inflammation associated with obesity can lead to metabolic alterations. As physical activity is an alternative to decrease excess weight and its related comorbidities, High-Intensity Interval Training (HIIT) has recently emerged as effective in regulating whole-body metabolism and inflam-matory processes in people with excess weight.The objective was to compare the effects of a modified HIIT program on peripheral blood leukocytes (PBL), metabolic profile, insulin resistance (IR), andbody composition (BC) in sed-entary adults with excess weight. PBL, biochemical variables, IR, and BC were analyzed in 37 participants, 23 sedentary young adults (17 with overweight and six with obesity), before and after eight weeks of a modified HIIT program and compared with those of 14 healthy-weight participants. The results showed that after HIIT, total lymphocytes, TCD3+, and TCD8+ lymphocytes decreased; granulocytes and naïve TCD3+ cells increased in patients. Regarding partial correlations, we found that changes (Δ) in TCD8+ lymphocytes correlated posi-tively with glucose and LDL -c, while naïve TCD3+ cells correlated with total cholesterol and LDL -c. Δ in TCD4+CD45RA+ cells correlated negatively with Δ in subcutaneous fat tissue and body fat mass. This study reports that sedentary young adults who completed the modified HIIT program showed lymphocyte levels similar to those in healthy-weight individuals and positive changes in the study variables. Such changes suggest immunometabolic regulation through the implementation of HIIT in participants with overweight and obesity.

Milkshake Acutely Stimulates Dopamine Release in Ventral and Dorsal Striatum in Healthy-Weight Individuals and Patients with Severe Obesity Undergoing Bariatric Surgery: A Pilot Study.

The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [11C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum (p = 0.032), posterior putamen (p = 0.012), and anterior caudate (p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.

Lipidomics Profiling and Risk of Coronary Artery Disease in the BioHEART-CT Discovery Cohort

The current coronary artery disease (CAD) risk scores for predicting future cardiovascular events rely on well-recognized traditional cardiovascular risk factors derived from a population level but often fail individuals, with up to 25% of first-time heart attack patients having no risk factors. Non-invasive imaging technology can directly measure coronary artery plaque burden. With an advanced lipidomic measurement methodology, for the first time, we aim to identify lipidomic biomarkers to enable intervention before cardiovascular events. With 994 participants from BioHEART-CT Discovery Cohort, we collected clinical data and performed high-performance liquid chromatography with mass spectrometry to determine concentrations of 683 plasma lipid species. Statin-naive participants were selected based on subclinical CAD (sCAD) categories as the analytical cohort (n = 580), with sCAD+ (n = 243) compared to sCAD− (n = 337). Through a machine learning approach, we built a lipid risk score (LRS) and compared the performance of the existing Framingham Risk Score (FRS) in predicting sCAD+. We obtained individual classifiability scores and determined Body Mass Index (BMI) as the modifying variable. FRS and LRS models achieved similar areas under the receiver operating characteristic curve (AUC) in predicting the validation cohort. LRS enhanced the prediction of sCAD+ in the healthy-weight group (BMI &lt; 25 kg/m2), where FRS performed poorly and identified individuals at risk that FRS missed. Lipid features have strong potential as biomarkers to predict CAD plaque burden and can identify residual risk not captured by traditional risk factors/scores. LRS compliments FRS in prediction and has the most significant benefit in healthy-weight individuals.

Metabolically Healthy Overweight and Obesity, Transition to Metabolically Unhealthy Status and Cognitive Function: Results from the Framingham Offspring Study.

To evaluate the association between metabolically healthy overweight/obesity (MHO) status and longitudinal cognitive function while also considering the stability of the condition. In total, 2892 participants (mean age 60.7 (9.4) years) from Framingham Offspring Study completed health assessments every four years since 1971. Neuropsychological testing was repeated every four years starting from 1999 (Exam 7) to 2014 (Exam 9) (mean follow-up: 12.9 (3.5) years). Standardized neuropsychological tests were constructed into three factor scores (general cognitive performance, memory, processing speed/executive function). Healthy metabolic status was defined as the absence of all NCEP ATP III (2005) criteria (excluding waist circumference). MHO participants who scored positively for one or more of NCEP ATPIII parameters in the follow-up period were defined as unresilient MHO. No significant difference on the change in cognitive function over time was observed between MHO and metabolically healthy normal weight (MHN) individuals (all p > 0.05). However, a lower processing speed/executive functioning scale score was observed in unresilient MHO participants compared to resilient MHO participants (β = -0.76; 95% CI = -1.44, -0.08; p = 0.030). Retaining a healthy metabolic status over time represents a more important discriminant in shaping cognitive function compared to body weight alone.

Investigating family history of diabetes as a predictor of fasting insulin and fasting glucose activity in a sample of healthy weight adults.

Type 2 diabetes is a major public health problem for the global community. Having a family history of diabetes significantly increases risk for diabetes development and understanding how family history contributes to diabetes risk could lead to more effective prevention efforts for at-risk individuals. In a previous study, we showed family history of diabetes is a significant predictor of fasting insulin in healthy weight children. The present study aimed to use the National Health and Nutrition Examination Survey (NHANES 2017) to apply similar multiple regression models to a population of healthy weight adults to determine if family history is a significant predictor of fasting glucose and fasting insulin. Fasting glucose (mg/dL) and fasting insulin (pmol/L) were used as dependent variables in each model, respectively, with family history of diabetes as the independent variable. Covariates for each model included age, gender, race/ethnicity, waist circumference, and macronutrient intake. The model significantly predicted the variance of fasting glucose [(F(11,364) = 34.80, p < 0.001, R2 = 0.2342] and fasting insulin [F(11,343) = 17.58, p < 0.001, R2 = 0.1162]. After adjusting for covariates, family history was a significant predicator of fasting glucose (p = 0.0193) as well as age, gender, non-Hispanic black ethnicity, waist circumference, and fat intake. Significant predictors of fasting insulin included gender and waist circumference, but not family history (p = 0.8264). In addition, fasting glucose was higher in individuals with a family history of diabetes (p = 0.033). These results add to the understanding of how family history influences the biomarkers that contribute to diabetes development. Knowledge of how family history of diabetes relates to fasting insulin and fasting glucose activity in healthy weight individuals can be used to design personalized screening and early prevention strategies.