Age of obesity onset affects subcutaneous adipose tissue cellularity differently in the abdominal and femoral region.

OBJECTIVE: We aimed to examine the effect of age of obesity onset, sex, and their interaction on abdominal and femoral subcutaneous adipose tissue (SAT) morphology (degree of adipocyte hyperplasia or hypertrophy). METHODS: In this cross-sectional study, we isolated adipocytes via collagenase digestion from abdominal and femoral SAT biopsies taken from male and female adults with childhood-onset obesity (CO; n = 8 males, n = 16 females) or adult-onset obesity (AO; n = 8 males, n = 13 females). Regional body composition was measured with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan. Mean adipocyte size was measured in abdominal and femoral SAT and was used to quantify morphology in android and gynoid subcutaneous fat, respectively. RESULTS: Abdominal SAT morphology was more hyperplastic in females with CO than females with AO (p = 0.004) but did not differ between males with CO and males with AO (p = 0.996). Conversely, femoral SAT morphology was more hypertrophic in males and females with CO than those with AO. CONCLUSIONS: Age of obesity onset appears to affect SAT morphology differently in the abdominal and femoral regions of male and female adults. Our findings challenge the notion that SAT is uniformly hyperplastic in CO and hypertrophic in AO.

Improvements in cardiorespiratory fitness, muscle strength and body composition to modest weight loss are similar in those with adult- versus childhood-onset obesity.

Adults who have had obesity from childhood are at greater risk of obesity-related comorbidities compared to those who only develop obesity in adulthood. The main way of mitigating these risks in obesity is with weight loss, which has been shown to positively affect the cardiorespiratory fitness (CRF) and body composition of adults. However, it is unclear whether the response of these outcomes to weight loss may be influenced by age of obesity onset. The objective of our study was to investigate how age of obesity onset mitigates the responsiveness of CRF, muscle strength and body composition to modest weight loss. Measurements were conducted at baseline and 12 weeks. In total, 37 participants (childhood-onset = 19, adult-onset = 18) lost 3.7% ± 0.4% through aerobic exercise and diet. The YMCA cycle ergometer test (YMCA) and the 20-m shuttle run test (20MSR) were used to estimate CRF (mL kg-1 min-1 ) and a handgrip dynamometer was used to estimate muscle strength. Total body composition was assessed by dual-energy x-ray absorptiometry (DEXA). Overall, CRF and body composition improved (time effect: p < 0.05) after 12 weeks. There was no group-by-time interaction for YMCA, 20MSR, muscle strength and body composition variables. Therefore, the present study suggests that individuals with childhood-onset obesity and adult-onset obesity can improve their CRF and body composition similarly after mild weight loss.

Compensatory health motivations and behaviors scale: Development, evaluation, psychometric properties and a preliminary validation.

The "Compensatory Health Beliefs" scale assesses the degree to which one believes that unhealthy behaviours can be compensated through healthier ones. However, no validated scale to assess compensatory weight-related behaviors exists. The study's objective was to develop (Study 1) and validate (Study 2) a questionnaire measuring compensatory health motivations and behaviors (CHMB) and to assess their associations with body mass index (BMI) and psychological weight-related measures. An initial 34-item measure was constructed based on a target sample's (Study 1, n = 158) suggestions and refined based on expert feedback. The measure was then tested in a representative Canadian adult sample (N = 1400, 48.7% male). The sample was stratified by sex and age and then randomly split into two (N = 701 for exploratory factor analysis; N = 699 for confirmatory factor analysis (CFA) cross-validation). Fit indices, standardized Cronbach's alphas and the associations between the CHMB model with cognitive restraint, weight concerns, and BMI were assessed in multiple linear regression models controlling for age and sex. The final CHMB model (n = 17 items) consisted of four subscales: (1) motivation, (2) use on special occasions, (3) general use, (4) compensatory health beliefs. Fit indices (Goodness of Fit Index = 0.922) and Cronbach's alphas were good (α = 0.88). In multiple linear regression models, all CHMB subscales were associated with greater cognitive restraint in eating. Compensatory behavior use on special occasions was associated with greater weight concern (B = 0.12, p < .0001), while general compensatory behavior use was associated with lower weight concern (B = -0.07, p < .05). None of the subscales were associated with BMI. The validated CHMB scale allows for the assessment of compensatory health motivations and behaviors in a Canadian population. Research on whether this scale can predict weight changes and general health is needed.

Senescence markers in subcutaneous preadipocytes differ in childhood- versus adult-onset obesity before and after weight loss.

OBJECTIVE: The aim of this study was to determine the effect of age of obesity onset on senescence-related markers in abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) before and after moderate (~10%) weight loss. METHODS: AB and FEM SAT were collected from human females with childhood-onset obesity (CO) or adult-onset obesity (AO) before and after diet- and exercise-induced weight loss. Immunofluorescence analysis of γH2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated ß-galactosidase (SA-ß-gal) activity was measured in SAT. RESULTS: CO had proportionately more AB and FEM preadipocytes with DNA damage (γH2AX+ ) and senescence markers (p53+ and/or p21+ ) than AO at baseline. The proportion of γH2AX+ FEM preadipocytes declined with weight loss in CO and was similar between groups after weight loss. The number of γH2AX foci in γH2AX+ preadipocytes decreased similarly between groups and regions with weight loss in parallel with an increase in RAD51. The proportion of p53+ and p21+ preadipocytes and SA-ß-gal+ cells in SAT did not change with weight loss, but the total p21 intensity in p53+ /p21+ FEM preadipocytes declined in AO. CONCLUSIONS: These results provide preliminary evidence that females with CO have an accelerated preadipocyte aging state that improves with weight loss in terms of DNA damage but not senescence.

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

BACKGROUND: Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. OBJECTIVES: To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. SETTING: University hospital. METHODS: A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. RESULTS: The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). CONCLUSIONS: The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Body-composition phenotypes and their associations with cardiometabolic risks and health behaviours in a representative general US sample.

Body mass index is poor at distinguishing between adiposity and muscle. Based on dual energy X-ray absorptiometry data, a diagnostic framework to analyze body composition by categorizing fat- and muscle-mass body composition into four phenotypes has been proposed. The objective of this study was to assess the association between body-composition phenotypes with adiposity measures, health behaviours and cardiometabolic risks in a representative U.S. adult population. Data were from NHANES (1999-2006: n = 9867; 2011-2018: n = 10,454). Four phenotypes based on being above/below the 50th percentile of age- and sex- adjusted reference curves of fat-mass and muscle-mass were identified. Multiple linear and logistic regressions were used to assess phenotypes (high [H] or low [L] adiposity [A] or muscle mass [M]) against adiposity measures, health behaviours, cardiometabolic risk, and dietary intake. Low-adiposity/high-muscle (LA-HM) was the referent. Analyses incorporated the complex sampling design and survey weights, and were adjusted for age, sex, race, and education. Compared to the LA-HM reference group, the HA-LM phenotype was less physically active, had higher total and lower high-density lipoprotein cholesterol, and had lower intake of all examined nutrients (all p < 0.01). For the HA-HM phenotype, unfavourable values were detected for all adiposity and cardiometabolic measures compared to the LA-HM phenotype (all p < 0.01). The two high adiposity phenotypes were associated with poorer health behaviours and cardiovascular risk factors, regardless of muscle-mass, but associations differed across the phenotypes. Results further underscores the importance of accounting for both adiposity and muscle mass in measurement and analysis. Further longitudinal investigation is needed.

Modified Delphi Process to Identify Research Priorities and Measures for Adult Lifestyle Programs to Address Type 2 Diabetes and Other Cardiometabolic Risk Conditions.

OBJECTIVES: Clinical and community guidelines recommend lifestyle (i.e. diet and physical activity) interventions for cardiometabolic conditions (including type 2 diabetes), yet current evidence suggests limited and variable services in primary care and public health settings. New implementation research studies are needed to ensure maximal effectiveness, equity and efficiency across all population subgroups and within the context of health systems. Such work will benefit from use of similar core measures and outcome indicators across studies. This Delphi process was undertaken by a new interdisciplinary volunteer researcher network to identify research priorities and core measures for such studies. METHODS: Interested network members completed 2 rounds of a modified Delphi process delivered through online questionnaire and teleconferences. Consensus was defined as the median and interquartile range within the top third of a 9-point scale. RESULTS: Twenty-five of 53 (47%) members and 18 (34%) participants completed the round 1 and round 2 surveys, respectively. Of 22 possible research priorities, 4 were rated high priority with consensus, including evaluating the efficacy and effectiveness of interventions in place, improving existing interventions for sustainability and clinical and public health research to advance existing knowledge to develop new capacities. Only 15 of the 93 measures and indicators proposed achieved similar consensus. CONCLUSIONS: This first effort confirms broad agreement on research priorities and limited agreement on core indicators/measures. The results provide a starting point for further development of common measures for implementation research in lifestyle studies addressing cardiometabolic conditions.

Sex differences in regional adipose tissue depots pose different threats for the development of Type 2 diabetes in males and females.

Type 2 diabetes mellitus (T2DM) affects males and females disproportionately. In midlife, more males have T2DM than females. The sex difference in T2DM prevalence is, in part, explained by differences in regional adipose tissue characteristics. With obesity, changes to regional adipokine and cytokine release increases the risk of T2DM in both males and females with males having greater levels of TNFα and females having greater levels of leptin, CRP, and adiponectin. Regional immune cell infiltration appears to be pathogenic in both sexes via different routes as males with obesity have greater VAT ATM and a decrease in the protective Treg cells, whereas females have greater SAT ATM and T cells. Lastly, the ability of female adipose tissue to expand all regions through hyperplasia, rather than hypertrophy, protects them against the development of large insulin-resistant adipocytes that dominate male adipose tissue. The objective of this review is to discuss how sex may affect regional differences in adipose tissue characteristics and how these differences may distinguish the development of T2DM in males and females. In doing so, we will show that the origins of T2DM development differ between males and females.

Adiposity and muscle mass phenotyping is not superior to BMI in detecting cardiometabolic risk in a cross-sectional study.

OBJECTIVE: Classifying adiposity based on dual-energy x-ray absorptiometry (DXA) muscle and fat mass phenotypes has been proposed. Whether these phenotypes are more accurate in predicting cardiometabolic risk than BMI weight status is unknown. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES; 1999-2006 cycles, n = 5,475). Weight status was defined by BMI. Phenotypes of adiposity and muscle were based on high (≥50th percentile) and low (<50th percentile) permutations of sex- and age-specific fat and muscle mass population curves. The area under the curves of receiver operating characteristic curves (ROC-AUCs), which predicted the presence of abnormal lipids, glucose, and blood pressure, were compared. All analyses were stratified by sex and incorporated the complex survey design and weighting of NHANES. RESULTS: The ROC-AUCs from weight status models used to correctly identify cardiometabolic risk ranged from 0.57 to 0.68, indicating generally weak predictive power. However, the ROC-AUCs from DXA phenotypes were lower (ranging from 0.53-0.68), indicating weaker predictive power than weight status, and were statistically inferior for nearly all of the comparisons. CONCLUSIONS: Despite DXA's high cost and detailed output regarding body composition, its phenotype classification was inferior to weight status in predicting cardiometabolic risk. Further studies investigating the utility of the phenotypes are needed.

Assessing the contribution of traditional foods to food security for the Wapekeka First Nation of Canada.

The food security crisis and disproportionately high burden of dietary related disease amongst northern Indigenous populations in Canada continues to be a troubling reality with little sign of improvement. The Government of Canada is responding by developing programs to support local food initiatives for northern isolated communities. While such investments appear commendable, the impact of local food harvesting to improve food security has yet to be determined. While there are clear nutritional and cultural benefits to traditional food sources, communities face considerable barriers acquiring it in sufficient amounts because of historically imposed lifestyle changes that have increased food insecurity rates. This study responds by providing a novel multidisciplinary approach that draws from firsthand experiences working with First Nations community members in a remote subarctic region in northwestern, Ontario, to estimate their community's total food requirement and the amount of wild animal food sources needed to sustain yearly food intake. This transferrable energy demand approach will be critical for policy makers to put into perspective the amount of wild food needed to have an impact on food security rates and ultimately improve dietary related diseases. Novelty: Provide government policy makers information about current harvest yields in a remote northern First Nation to understand the potential contribution of traditional food to improve local food security. Provide Indigenous communities a means to assess local food resources to measure the caloric contributions of traditional foods toward household food security.

Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids.

With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.

Substrate Oxidation Is Altered by Obesity During Submaximal Cycling in Prepubertal and Early Pubertal Children: A Quality Study.

BACKGROUND: To examine substrate oxidation in prepubertal and early pubertal children as a function of body weight, body composition, and sex during an exhaustive cycling test. METHODS: This study included 320 children in prepubertal and early puberty (Tanner stage 1 or 2; n = 188 males) who completed a minimum of 4 stages (2-5 min/stage) of an adapted version of the McMaster exhaustive exercise protocol on an upright cycle ergometer. Substrate utilization, relative to individual VO2peak, was determined using VO2 and VCO2 data, obtained with breath-by-breath gas analysis during exercise. RESULTS: Both peak (mg/kg lean body mass·min) and submaximal lipid oxidation (mg/kg lean body mass·min) were highest (P < .01) in children with healthy weight (HW), then overweight, and lowest in obese (OB). Both females with HW (compared with males with HW) and females with OB (compared with males with OB) had higher (P < .01) peak and submaximal lipid oxidation. In children with OB, fat-free mass correlated positively (P < .01) with submaximal lipid oxidation (r = .50). In contrast, in children with HW and overweight, fat-free mass correlated positively (P < .01) with carbohydrate oxidation (r = .52 and r = .47, respectively). CONCLUSION: Obesity during childhood may alter substrate oxidation during exercise. These results may have implications in the implementation of exercise programs in prepubertal or early puberty to control adiposity.

Association between rs174537 FADS1 polymorphism and immune cell profiles in abdominal and femoral subcutaneous adipose tissue: an exploratory study in adults with obesity.

Fatty acid desaturase 1 (FADS1) polymorphisms alter fatty acid content in subcutaneous adipose tissue (SAT); however, existing evidence is limited and conflicting regarding the association between FADS1 variants and SAT inflammatory status. To advance this area, we conducted an exploratory study to investigate whether the common rs174537 polymorphism in FADS1 was associated with immune cell profiles in abdominal and femoral SAT in individuals with obesity. FADS1 gene expression and immune cell profiles in SAT depots were assessed by qPCR and flow cytometry, respectively. Although FADS1 gene expression was associated with genotype, no associations were observed with immune cell profiles in either depot. Our study provides additional evidence that rs174537 in FADS1 has minimal impact on inflammatory status in obese SAT.

A reliable, reproducible flow cytometry protocol for immune cell quantification in human adipose tissue.

The ability to accurately identify and quantify immune cell populations within adipose tissue is important in understanding the role of immune cells in metabolic disease risk. Flow cytometry is the gold standard method for immune cell quantification. However, quantification of immune cells from adipose tissue presents a number of challenges because of the complexities of working with an oily substance and the rapid deterioration of immune cell viability before analysis can be performed. Here we present a highly reproducible flow cytometry protocol for the quantification of immune cells in human adipose tissue, which overcomes these issues.

Methodological considerations for the measurement of arterial stiffness using applanation tonometry.

INTRODUCTION: Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value. METHODS: Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots. RESULTS: Participants' mean age was 50 ±â€Š14 years and BMI was 28.0 ±â€Š5.5 kg/m2 (N = 306, 79% women). The overall mean difference was -0.10 m/s (95% CI 0.17 to -0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values. CONCLUSION: Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.

Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity.

OBJECTIVE: The inflammatory environment in lower-body subcutaneous adipose tissue (SAT) has been largely unexplored. This study aimed to examine the effects of region (upper body vs. lower body) and sex on SAT immune cell profiles in young adults with obesity. METHODS: Abdominal (AB) and femoral (FEM) SAT was collected from 12 males (mean [SEM] age = 30.8 [1.4] years; mean [SEM] BMI = 34.1 [1.1] kg/m2 ) and 22 females (mean [SEM] age = 30.6 [0.6] years; mean [SEM] BMI = 34.0 [0.7] kg/m2 ) with obesity via needle aspiration. Flow cytometry was used to quantify macrophage (CD68+) and T-cell (CD3+) subpopulations in the stromovascular fraction of each SAT region. RESULTS: Females had a greater proportion of most T-cell types (CD3+CD4+CD45RA+, CD3+CD4+CD45RA-, and CD3+CD8+CD45RA+) in FEM compared with AB SAT, while males had similar proportions in both regions. Regardless of sex, the M1-like macrophage population (CD68+CD206-) was proportionally higher in AB SAT than in FEM SAT. CONCLUSIONS: Results showed that T-cell populations vary by SAT region in females but not males. Both sexes, however, have proportionately more proinflammatory macrophages in upper-body than in lower-body SAT. It remains to be seen how these unique immune cell profiles in males and females with obesity contribute to adipose tissue inflammation and metabolic disease risk.

Acetyl-CoA Regulation, OXPHOS Integrity and Leptin Levels Are Different in Females With Childhood vs Adulthood Onset of Obesity.

Although childhood-onset obesity (CO) and adulthood-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and to identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using dual-energy x-ray absorptiometry (DXA) and computed tomography. Levels of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared with CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin concentrations was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEP expression in adipose tissue, and circulating leptin in AO. NAD+/NADH was higher in CO; however, abundance of mitochondrial complexes, the complex II:complex V ratio, and the complex IV:complex V ratio were lower in CO, reflecting compromised mitochondrial function in subcutaneous adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate acetyl-CoA between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in humans.

Obesity and ageing: Two sides of the same coin.

Conditions and comorbidities of obesity mirror those of ageing and age-related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are "two sides of the same coin" through discussing how obesity predisposes an individual to age-related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early-onset of chronic diseases in obesity parallel those of ageing.