Role Of Adiposity Research Articles

Artificial intelligence measured 3D lumbosacral body composition and clinical outcomes in rectal cancer patients.

Patient body composition (BC) has been shown to help predict clinical outcomes in rectal cancer patients. Artificial intelligence algorithms have allowed for easier acquisition of BC measurements, creating a comprehensive BC profile in patients using data from an entire three-dimensional (3D) region of the body. This study has utilized AI technology to measure BC from the entire lumbosacral (L1-S5) region and assessed the associations between BC and clinical outcomes in rectal cancer patients who have undergone neoadjuvant therapy followed by surgery. A retrospective, cross sectional analysis was performed on locally advanced rectal cancer (LARC) patients treated with neoadjuvant long-course chemoradiotherapy followed by curative resection with total mesorectal excision at a tertiary referral centre, Western Health, Melbourne, Australia. A pre-trained and validated in-house AI segmentation model was used to automatically segment and measure intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and skeletal muscle (SM) from CT slices across the entire L1-S5 level of each patient. Multivariate analysis between patient BC and clinical outcomes was performed. Two hundred and fourteen patients were included in the study. One hundred and fifty-one (70.6%) patients were male and 63 (29.4%) patients were female. The average age at diagnosis was 62.4 (±12.7) years. SM density, but not volume, was associated with better overall survival (OS) (HR 0.24, P = 0.029), recurrence-free survival (RFS) (HR 0.45, P = 0.048) and decreased length of stay (LoS) (HR 1.58, P = 0.036). Both IMAT volume (HR 0.13, P = 0.008) and density (HR 0.26, P = 0.006) were associated with better OS. This study measured 3D BC from the entire lumbosacral region of rectal cancer patients. SM density was the most significant BC parameter, and was associated with improved OS, RFS and LoS. This adds to growing evidence that SM is a key component of BC in cancer patients and should be optimized prior to treatment. IMAT was also a prognostic factor, giving rise to avenues of future research into the role of adiposity on nutrition and tumour immunology.

244 - The role of overweight and obesity in explaining perinatal outcome differences between women with type 1 and type 2 diabetes

244 - The role of overweight and obesity in explaining perinatal outcome differences between women with type 1 and type 2 diabetes

Metabolic dysfunction-associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity.

Nonalcoholic fatty liver disease (NAFLD) has recently been renamed metabolic dysfunction-associated fatty liver disease (MAFLD) by international consensus. Both MAFLD and osteoporosis are highly prevalent metabolic diseases. Recent evidence indicates that NAFLD increases the risk of low bone mineral density and osteoporosis, likely mediated by obesity. NAFLD has a close association with obesity and other metabolic disorders. Although obesity was previously thought to protect against bone loss, it now heightens osteoporotic fracture risk. This overview summarizes current clinical correlations between obesity, NAFLD, and osteoporosis, with a focus on recent insights into potential mechanisms interconnecting these three conditions. This study reviewed the scientific literature on the relationship between obesity, nonalcoholic fatty liver disease, and osteoporosis as well as the scientific literature that reveals the underlying pathophysiologic mechanisms between the three. Emerging evidence suggests obesity plays a key role in mediating the relationship between NAFLD and osteoporosis. Accumulating laboratory evidence supports plausible pathophysiological links between obesity, NAFLD, and osteoporosis, including inflammatory pathways, insulin resistance, gut microbiota dysbiosis, bone marrow adiposity, and alterations in insulin-like growth factor-1 signaling. Adiposity has important associations with NAFLD and osteoporosis, the underlying pathophysiologic mechanisms between the three may provide new therapeutic targets for this complex patient population.

Changes in Body Weight and Risk Factors for Overweight and Obesity in 5-6-Year-Old Children Attending School in Geneva.

Background: The prevalence of obesity and overweight in children is increasing in industrialized countries. Monitoring the evolution of these phenomena is essential for understanding prevention and health promotion programs. This study aims to present the analysis of anthropometric data collected by school nurses from the School Health Service of Geneva (Service de santé de l'enfance et de la jeunesse) for children aged 5 to 6 years during the 2021-2022 school year, as well as describe the trends in overweight and obesity from 2003-2004 to 2021-2022. Risk factors were also assessed in the 2021-2022 sample. Methods: This study included a random sample of 958 (479 girls and 479 boys) primary school pupils aged 5 to 6 years in Geneva. Data on weight, height and socioeconomic status were collected. BMI was analyzed using the Cole standard. A multivariate analysis was conducted to assess the influence of socioeconomic factors on overweight and obesity. We compared these results with BMI trends in students of the same age since 2003. Results: In 2021-2022, overall prevalence of overweight was 12.73%, and obesity was 5.64%. Girls had higher rates of overweight (14.20%) and obesity (6.68%) compared to boys (11.27% and 4.59%, respectively) (p < 0.0001). Overweight in boys significantly increased since the 2013-2014 and 2019-2020 measurements (p = 0.003). The trend for girls was similar but not statistically significant. Obesity rates have not significantly increased since 2019-2020 in both genders, but there is a significantly increasing trend for girls since 2013-2014 p = 0.045). Socioeconomic factors, particularly the socioeconomic class of parents, played a predictive role in overweight and obesity. Conclusions: The School Health Service of Geneva and the Directorate General of Health have a crucial role in monitoring and preventing childhood obesity. The prevalence of overweight and obesity has remained high since 2010, justifying continuous efforts for prevention. A significant increase in prevalence has been observed since 2020, particularly among overweight boys, and could be related to COVID-19 confinement measures.

Adipose c-Jun NH2-terminal kinase promotes angiotensin II-induced and deoxycorticosterone acetate salt-induced hypertension and vascular dysfunction by inhibition of adiponectin production and activation of SGK1 in mice.

Adipose c-Jun NH2-terminal kinase 1/2 (JNK1/2) is a central mediator involved in the development of obesity and its complications. However, the roles of adipose JNK1/2 in hypertension remain elusive. Here we explored the role of adipose JNK1/2 in hypertension. The roles of adipose JNK1/2 in hypertension were investigated by evaluating the impact of adipose JNK1/2 inactivation in both angiotensin II (Ang II)-induced and deoxycorticosterone acetate (DOCA) salt-induced hypertensive mice. Specific inactivation of JNK1/2 in adipocytes significantly alleviates Ang II-induced and DOCA salt-induced hypertension and target organ damage in mice. Interestingly, such beneficial effects are also observed in hypertensive mice after oral administration of JNK1/2 inhibitor SP600125. Mechanistically, adipose JNK1/2 acts on adipocytes to reduce the production of adiponectin (APN), then leads to promote serum and glucocorticoid-regulated kinase 1 (SGK1) phosphorylation and increases epithelial Na + channel α-subunit (ENaCα) expression in both renal cells and adipocytes, respectively, finally exacerbates Na + retention. In addition, chronic treatment of recombinant mouse APN significantly augments the beneficial effects of adipose JNK1/2 inactivation in DOCA salt-induced hypertension. By contrast, the blood pressure-lowering effects of adipose JNK1/2 inactivation are abrogated by adenovirus-mediated SGK1 overexpression in Ang II -treated adipose JNK1/2 inactivation mice. Adipose JNK1/2 promotes hypertension and targets organ impairment via fine-tuning the multiorgan crosstalk among adipose tissue, kidney, and blood vessels.

Genetic variation in TAS2R38 bitterness receptor is associated with body composition in Korean females

Bitterness-receptor gene TAS2R38 is associated with taste sensitivity and dietary behaviour, and is known to play a critical role in adiposity. However, evidence regarding body composition from a large cohort is lacking. This study aimed to ascertain whether TAS2R38 rs10246939 C > T bitterness genetic variation is associated with body composition in Korean individuals. The TAS2R38 rs10246939 genotypes, anthropometric measurements, and body composition of 1,843 males and 1,801 females from the Korean Genome and Epidemiology Study were analysed. Findings suggested that there was a significant difference in body fat components by TAS2R38 genotype. Furthermore, the bitterness genotype exhibited a positive association with adiposity markers in females. The TT genotype showed greater body mass index, body fat percentage, and degree of obesity than those with the C allele. However, such an association was not observed in males. In conclusion, this study suggests that TAS2R38 rs10246939 is associated with fat tissue markers in Korean females.

Abstract 16797: The Role of Adiposity on Microvascular Dysfunction and Arterial Stiffness in Patients With New Onset Breast Cancer

INTRODUCTION: Increased adiposity is a risk factor for both cardiovascular disease (CVD) and cancer. Microvascular endothelial dysfunction and arterial stiffness are independent risk factors for CVD and can accelerate vascular aging. Whether or not adiposity plays a role in vascular aging over time in patients with new-onset breast cancer (BC) has yet to be elucidated. Hypothesis: Adiposity impacts microvascular dysfunction and arterial stiffness differently in women undergoing therapy for recent BC diagnoses. Methods: Two lean (L; BMI &lt; 25 kg/m 2 ) and four overweight and obese (Ow/Ob; BMI &gt; 25 kg/m 2 ) women diagnosed with BC within the last 3 months participated in the study. Using laser Doppler imaging, microvascular endothelial function was assessed with three protocols: 1) cutaneous post-occlusion reactive hyperemia (PORH), 2) local thermal heating (LTH), and 3) iontophoresis of acetylcholine. Arterial stiffness was assessed using pulse wave velocity (PWV) and pulse wave analysis (PWA). Assessments were made at baseline and at 3 and 6 months following enrollment. Data are reported as means ± SE. Results: No differences in age, height, blood pressure, or total cholesterol (all p &gt;0.05) were observed between L and Ow/Ob groups. Microvascular function and arterial stiffness were similar at baseline between groups. There was a greater decrease in LTH responses from baseline to 6 months post-baseline in Ow/Ob women (Δ-48±4 PU; p =0.001) compared to L women (Δ-16±13 PU; p =0.125). Similar responses in both groups were noted for PORH ( p =0.886) and iontophoresis ( p =0.784). PWV was similar from baseline to 6 months post-baseline in both groups; however, the PWA tended to increase over time in Ow/Ob women (Δ2.5±4.7) and decrease in L women (Δ-3.0±5.0). CONCLUSION: Ow/Ob women have a greater rate of decline in LTH responses compared with L women, whereas similar responses between L and OW/OB women were observed over time for PORH and iontophoresis. In addition, central aortic stiffness increased in Ow/Ob women and decreased in L women, while no change in PWV was observed. These findings suggest that adiposity may impact vascular beds differently over time following the initial diagnosis of breast cancer.

Prevalence of overweight and obesity in patients with major depressive disorder with anxiety: Mediating role of thyroid hormones and metabolic parameters

BackgroundsAnxiety is a common comorbidity in major depressive disorder (MDD); however, its role in overweight and obesity in MDD patients remains unclear. We examined the relationship between severe anxiety and overweight and obesity, as well as the mediating role of thyroid hormones and metabolic parameters in MDD patients. MethodsThis cross-sectional study recruited 1718 first-episode drug-naïve MDD outpatients. All participants were rated on the Hamilton Depression Rating Scale for depression and Hamilton Anxiety Rating Scale for anxiety and measured in thyroid hormones and metabolic parameters. ResultsA total of 218 (12.7 %) individuals had severe anxiety. The prevalence of overweight and obesity in patients with severe anxiety was 62.8 % and 5.5 %, respectively. Severe anxiety symptoms were associated with overweight (Odds Ratio [OR]: 1.47, 95 % CI: 1.08, 2.00) and obesity (OR: 2.10, 95 % CI: 1.07, 4.15). The association between severe anxiety and overweight was mainly attenuated by thyroid hormones (40.4 %), blood pressure (31.9 %), and plasma glucose (19.1 %). For obesity, the association with severe anxiety was mainly attenuated by thyroid hormones (48.2 %), blood pressure (39.1 %), and total cholesterol (28.2 %). LimitationsDue to the cross-sectional design, no causal relationship could be derived. ConclusionsThyroid hormones and metabolic parameters can explain the risk of overweight and obesity associated with severe anxiety in MDD patients. These findings add to the knowledge of the pathological pathway of overweight and obesity in MDD patients with comorbid severe anxiety.

Sedentariness and overweight in relation to mortality in sub-Saharan Africa. A mediation analysis based on the World Health Organization-Global Health Observatory data repository.

Globally, noncommunicable diseases (NCDs) have been continuously reported to be the number one leading cause of reduced life expectancy and poor life quality and have thus become a major public health concern. This study aimed to investigate the complex mediation analysis between physical inactivity and overweight in relation to mortality. The study is based on public data collected by the Global Health Observatory of the World Health Organization. We showed that the median early mortality attributable to NCDs during the period 2016-2019 in both men and women was 23.2% (5th to 95th range=17.2, 35.6) while that in men alone was 25.1% (16.5, 45.7) and that of women alone was 22.0% (17.0, 27.9). When considering regional early NCDs mortality for both men and women, a systematically high median was observed in Southern Africa [28.7% (22.2, 43.8)] and a low median in Eastern Africa [21.1% (17.15, 27.3)]. The analysis of the overall relation between physical inactivity, overweight and early mortality due to NCDs revealed a statistical significance of the direct association between physical inactivity and early mortality due to NCDs. Our findings revealed three main epidemiological and public health concerns. First, early mortality attributable to NCDs in a range of about 20 to 30% across the sub-Saharan African regions for both sexes was observed. Second, there was a direct effect between physical inactivity and early NCDs mortality as well as the indirect effect mediated by overweight. Finally, a percentage point decrease in physical inactivity prevalence and overweight could effectively generate a reduction in mortality due to NCDs. Future studies are needed to confirm the scientific evidence observed in this study. Such studies should be based on observation of individual subjects, adopt a longitudinal design, and collect information that evaluates the complex relationship between physical inactivity and early NCDs mortality, along with the role of overweight as a possible mediator.

Obesity Is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue whose primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. Metformin has demonstrated antitumorigenic properties both in pre-clinical and clinical studies. Nevertheless, its immunomodulating properties in BC are largely unknown. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance, and the immunometabolic role of metformin in BC. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes, leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. Metformin may play a role in the metabolic reprogramming of tumour-infiltrating immune cells that are dysregulated by systemic inflammation. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

Urban Youth Perceptions of Sports and Energy Drinks: Insights for Health Promotion Messaging.

This study aimed to examine urban adolescents' beliefs about sports and energy drinks to identify factors for health messaging to discourage youth consumption. Focus group study involving thirty-four adolescents in urban areas (12 female, 12 male, and 10 unreported sex; 19 Hispanic, 11 Non-Hispanic Black, 2 Asian, and 1 unknown race or ethnicity). Four focus groups were conducted with adolescents in urban areas. Each on-time moderated group discussion was structured to generate an inventory of attitudinal, normative and efficacy beliefs associated with sports and energy drink consumption and reduction. Thematic analysis was used to analyse the data. Attitudinal and normative beliefs were more positive towards sports drink consumption and energy drink reduction. Misperceptions about the need for sports drinks to avoid dehydration during physical activity were evident. Product accessibility and advertising pervasiveness were facilitators influencing consumption and barriers to reduction for both products. Results highlight important differences in perceptions about sports and energy drinks that indicate the need for different approaches and messages for interventions designed to curb consumption of these products. Recommendations for message design are provided.

Infant gross motor development and childhood physical activity: Role of adiposity

Later achievement of standing and walking in infancy predicts childhood physical inactivity. This study aimed to examine associations between ages of achieving six gross motor milestones and childhood physical activity, and whether these associations were mediated by adiposity. A retrospective analysis of a subset from a cohort study. Data were available for 211 first-grade primary school children (aged 6–7 years) in the Kanto region, Japan. Information on ages of achieving holding head up, sitting, crawling, standing supported, walking supported, and independent walking were obtained from parental records in the Maternal and Child Health Handbooks. Adiposity was assessed using dual-energy X-ray absorptiometry, and expressed as body fat percentage. Current gross motor skills were assessed by the Test of Gross Motor Development 2nd edition. Physical activity was measured using a triaxial accelerometer and defined as time involved in moderate-to-vigorous-intensity physical activity (MVPA). Multiple regression analyses revealed that the age of achieving standing supported was negatively associated with MVPA (p ​= ​.021), while ages of achieving crawling (p ​= ​.010), standing supported (p ​= ​.002), and walking supported (p ​= ​.033) were positively associated with adiposity, after adjusting for potential confounders including current gross motor skills. When adiposity was introduced as a covariate, the age of achieving standing supported was still associated with MVPA (p ​= ​.048), and the indirect effect of achievement of standing supported on MVPA was not significant. Infants who achieve standing supported at a later age are less likely to be active during early school age, and adiposity may not mediate this association.

In utero particulate matter exposure in association with newborn mitochondrial ND4L10550A>G heteroplasmy and its role in overweight during early childhood

BackgroundMitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5 exposure is associated with cord blood MT-ND4L10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>G heteroplasmy in overweight during early childhood is investigated.MethodsThis study included 386 mother-newborn pairs. Outdoor PM2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>G heteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5 exposure on childhood overweight mediated by cord blood MT-ND4L10550A>G heteroplasmy.ResultsPrenatal PM2.5 exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51; p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5 exposure was associated with cord blood MT-ND4L10550A>G heteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m3 increment in PM2.5 was linked with cord blood MT-ND4L10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>G heteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50; p = 0.02). The effect of prenatal PM2.5 exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>G heteroplasmy.ConclusionsCord blood MT-ND4L10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>G heteroplasmy in the association between PM2.5 exposure and childhood overweight.

Adiposity and cancer survival: a systematic review and meta-analysis.

The increasing availability of clinical imaging tests (especially CT and MRI) that directly quantify adipose tissue has led to a rapid increase in studies examining the relationship of visceral, subcutaneous, and overall adiposity to cancer survival. To summarize this emerging body of literature, we conducted a systematic review and meta-analysis of imaging-measured as well as anthropometric proxies for adipose tissue distribution and cancer survival across a wide range of cancer types. Using keywords related to adiposity, cancer, and survival, we conducted a systematic search of the literature in PubMed and MEDLINE, Embase, and Web of Science Core Collection databases from database inception to 30 June 2021. We used a random-effect method to calculate pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) within each cancer type and tested for heterogeneity using Cochran's Q test and the I2 test. We included 203 records for this review, of which 128 records were utilized for quantitative analysis among 10 cancer types: breast, colorectal, gastroesophageal, head and neck, hepatocellular carcinoma, lung, ovarian, pancreatic, prostate, and renal cancer. We found that imaging-measured visceral, subcutaneous, and total adiposity were not significantly associated with increased risk of overall mortality, death from primary cancer, or cancer progression among patients diagnosed with these 10 cancer types; however, we found significant or high heterogeneity for many cancer types. For example, heterogeneity was similarly high when the pooled HRs (95% CI) for overall mortality associated with visceral adiposity were essentially null as in 1.03 (0.55, 1.92; I2 = 58%) for breast, 0.99 (0.81, 1.21; I2 = 71%) for colorectal, versus when they demonstrated a potential increased risk 1.17 (0.85, 1.60; I2 = 78%) for hepatocellular carcinoma and 1.62 (0.90, 2.95; I2 = 84%) for renal cancer. Greater adiposity at diagnosis (directly measured by imaging) is not associated with worse survival among cancer survivors. However, heterogeneity and other potential limitations were noted across studies, suggesting differences in study design and adiposity measurement approaches, making interpretation of meta-analyses challenging. Future work to standardize imaging measurements and data analyses will strengthen research on the role of adiposity in cancer survival.

Adiposity in resectable colorectal cancer.

3614 Background: Sarcopenia and myosteatosis affect survival in colorectal cancer (CRC). The role of adiposity is not yet fully elucidated. This study explores visceral and subcutaneous adipose tissue (VAT/SAT) distributions, and how they affect overall (OS), disease-free (DFS) and cancer specific survival (CSS). Methods: This retrospective cohort study, included resected stage I-III CRC in Alberta from January 2007 to December 2009. We excluded recurrent/metastatic disease or no CT scan. This study was approved by the Health Research Ethics Board at the University of Alberta. Body composition parameters were measured from CT scans. Sarcopenia and myosteatosis were defined by cohort-specific cut-off values. Total and visceral fat areas were indexed by height, and cohort-specific cut-offs defined total and visceral obesity (VO). SAT (SC:TFR) and VAT (V:TFR) to total adipose ratios were compared by gender, as described by Fleming. SAT and VAT fat radiodensity (Hounsfield units, HU) was measured and divided into quartiles. Differences between groups were compared with student’s t-test and Fisher Exact test. Cox proportional hazard models were created, adjusting for important covariates, to assess adiposity effects on OS, DFS and CSS. Results: Our cohort included 968 patients with a median follow up of 63.5 months. The majority were stage II (38.6%) and III (51.0%). In total, 67.9% had total obesity and 51.0% had visceral obesity. In males, there was no difference in the incidence of myosteatosis or sarcopenia, regardless of V:TFR or SC:TFR. In women, those with a high V:TFR or SC:TFR had significantly higher incidence of myosteatosis, but not sarcopenia. Men and women with elevated V:TFR had significantly lower VAT and SAT HU (p&lt;0.001, p=0.0113). Those with elevated SC:TFR had significantly higher VAT and SAT HU (p&lt;0.001). VAT and SAT HU was lowest in those with myosteatosis alone (p&lt;0.001; p=0.005). In survival analysis, VO and VAT HU quartiles predicted worse OS in uni-, but not multivariate analysis. SAT HU quartiles predicted worse survival in uni- and multivariate analysis, with the highest quartile of SAT HU predicting increased risk of death (HR 1.35, p=0.037). Adiposity was not predictive of CSS or DFS in uni- or multivariate analysis. Conclusions: This study demonstrated changes in VAT/SAT in relation to well described body composition parameters. SAT HU may have a more important role in OS than visceral adipose characteristics, despite known metabolic characteristics of VAT. True roles of adipose tissue in CRC outcomes remains unclear. VAT/SAT measurements using cross-sectional imaging allows for a detailed analysis and understanding of how adiposity may affect survival. [Table: see text]

The role of adiposity, body mass index, aging and chronic comorbidities on the progression of COVID-19 illness. Is a ‘long COVID’ syndrome inevitable?

Age associated overweight and obese conditions now approach epidemic proportions in Westernized society, often beginning in childhood and extending throughout the lifespan. Excess adiposity is often linked to increased visceral fat deposition where it is associated with increases in the relative risks for developing severe complications of covid-19. Thus, excess adiposity, along with NIDDM, hypertension, respiratory, disordered bioenergetics and other comorbidities, may be added to a growing list of significant independent risk factors in the progression of complications in covid-19 illness in both vaccinated and unvaccinated individuals, and which may lead to the development of a syndrome of ‘long covid’ in a sizable proportion of those infected. In addition to excess adiposity, non-insulin dependent diabetes (NIDDM), hypertension, disordered bioenergetics, along with other commonly occurring age-related comorbidities contribute to a lengthy list of significant risk factors that often progress to complications in the development and treatment options for covid-19 illness. These complications may occur in both vaccinated and unvaccinated individuals and may lead to the development of a syndrome of ‘long covid’ in a sizable proportion of infected individuals. The coronavirus causing Covid-19, SARS-CoV-2 has some similarities to the emergence of earlier reports of other zoonotic coronavirus illnesses including MERS and SARS which also caused respiratory illness in humans also with chronic symptoms of fatigue, musculoskeletal pain and psychiatric impairments. The origin of SARS-Cov-2 remains unclear, but appears to have originated in Wuhan, China in late 2019 as a local epidemic but within a few months had spread throughout the globe and was declared a pandemic by the WHO within three months of its first report to the WHO in December 2019. The virus enters mammalian organ systems via ACE2 receptors of receptive tissues of the respiratory, gastrointestinal, and other organs including the adipose tissue that can interact with the infective spike protein domains of the virus thereby permitting cellular entry. Once the adipose tissue becomes infected, the virus begins to replicate vigorously and initiates the release of inflammatory cytokines including IL-6, TNF and others which can contribute to an often-fatal cytokine storm. The common clinical symptoms include fever, coughing, musculoskeletal pain, and profound fatigue, and which often progress to hyperinflammation, a potentially serious cytokine storm, an acute respiratory distress syndrome (ARDS) and covid-related coagulopathy (CAC) and are often observed in overweight or obese individuals following SARS-CoV-2 infection in the absence of other comorbidities. While weight loss toward a normalization of BMI and an otherwise healthy weight is associated with smaller adipocyte size and corresponding adipocyte surface area can decrease the relative risks for other comorbidities over time, the risk reduction for COVID-19 following weight loss remains unclear. In conclusion, progressive increases in adiposity, overweight and obese conditions that increase visceral fat deposition and may progressively increase the relative risk for the most severe complications and dire outcomes of COVID-19 illness.

The impact of obesity on the regulation of muscle blood flow during exercise in patients with heart failure with a preserved ejection fraction.

Obesity is now considered a primary comorbidity in heart failure with preserved ejection fraction (HFpEF) pathophysiology, mediated largely by systemic inflammation. Although there is accumulating evidence for a disease-related dysregulation of blood flow during exercise in this patient group, the role of obesity in the hemodynamic response to exercise remains largely unknown. Small muscle mass handgrip (HG) exercise was used to evaluate exercising muscle blood flow in nonobese (BMI < 30 kg/m2, n = 14) and obese (BMI > 30 kg/m2, n = 40) patients with HFpEF. Heart rate (HR), stroke index (SI), cardiac index (CI), mean arterial pressure (MAP), forearm blood flow (FBF), and vascular conductance (FVC) were assessed during progressive intermittent HG exercise [15%-30%-45% maximal voluntary contraction (MVC)]. Blood biomarkers of inflammation [C-reactive protein (CRP) and interleukin-6 (IL-6)] were also determined. Exercising FBF was reduced in obese patients with HFpEF at all work rates (15%: 304 ± 42 vs. 229 ± 15 mL/min; 30%: 402 ± 46 vs. 300 ± 18 mL/min; 45%: 484 ± 55 vs. 380 ± 23 mL/min, nonobese vs. obese, P = 0.025), and was negatively correlated with BMI (R = -0.47, P < 0.01). In contrast, no differences in central hemodynamics (HR, SI, CI, and MAP) were found between groups. Proinflammatory biomarkers were markedly elevated in patients with obesity (CRP: 2,133 ± 418 vs. 4,630 ± 590 ng/mL, P = 0.02; IL-6: 2.9 ± 0.3 vs. 5.2 ± 0.7 pg/mL, nonobese vs. obese, P = 0.04), and both biomarkers were positively correlated with BMI (CRP: R = 0.40, P = 0.03; IL-6: R = 0.57, P < 0.01). Together, these findings demonstrate the presence of obesity and an accompanying milieu of systemic inflammation as important factors in the dysregulation of exercising muscle blood flow in patients with HFpEF.NEW & NOTEWORTHY Obesity is the primary comorbid condition in HFpEF pathophysiology, but the role of adiposity on the peripheral circulation is not well understood. The present study identified a 30%-40% reduction in forearm blood flow during handgrip exercise, accompanied by a marked elevation in proinflammatory plasma biomarkers, in obese patients with HFpEF compared with their nonobese counterparts. These findings suggest an exaggerated dysregulation in exercising muscle blood flow associated with the obese HFpEF phenotype.

182 The role of diet during pregnancy in prevention of gestational diabetes mellitus

Introduction: Gestational diabetes mellitus (GDM) is characterised by glucose intolerance during pregnancy in previously normoglycemic women. The role of adiposity, diet, and physical activity before pregnancy is well known. However, pregnancy is a less well-studied period. This study’s aim was to examine the preventive potential of diet during pregnancy against GDM. Methods: Pregnant women were recruited from a private maternity hospital in Athens, Greece. They self-reported the carbohydrates-rich foods that they frequently consumed and the daily frequency of carbohydrates-rich meals and sweets both before and during pregnancy.

Accounting for the Origins and Toll of COVID 19 The key role of Overweight in COVID-19.

Both global and US data show associations between COVID-19 death rates and overweight or obesity, which are also risk factors for several other outcomes. Evidence suggests that among the strategies to reduce overweight and obesity are the simple actions of increasing fruit and vegetable consumption and physical activity. Potential benefits include saving thousands of lives and billions of dollars in a future pandemic and reduced risk of other chronic conditions.

Mendelian randomisation analyses of UK Biobank and published data suggest that increased adiposity lowers risk of breast and prostate cancer

Breast (BCa) and prostate (PrCa) cancer are the first and second most common types of cancer in women and men, respectively. We aimed to explore the causal effect of adiposity on BCa and PrCa risk in the UK Biobank and published data. We used Mendelian randomisation (MR) to assess the causal effect of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on BCa and PrCa risk. We found that increased BMI, WC and HC decreased the risk of breast cancer (OR 0.70 per 5.14 kg/m2 [0.59–0.85, p = 2.1 × 10–4], 0.76 per 12.49 cm [60–0.97, p = 0.028] and 0.73 per 10.31 cm [0.59–0.90, p = 3.7 × 10–3], respectively) and increased WC and BMI decreased the risk of prostate cancer (0.68 per 11.32 cm [0.50–0.91, p = 0.01] and 0.76 per 10.23 kg/m2 [0.61–0.95, p = 0.015], respectively) in UK Biobank participants. We confirmed our results with a two-sample-MR of published data. In conclusion, our results suggest a protective effect of adiposity on the risk of BCa and PrCa highlighting the need to re-evaluate the role of adiposity as cancer risk factor.