Long-term changes in adiposity markers during and after antidepressant therapy in a community cohort.

Research on antidepressant-related weight changes over more than 12 months is scarce and adjustment for the effects of depressive episodes has rarely been applied. Accordingly, our aim was to assess the associations of the use of any antidepressants, subclasses of antidepressant and specific compounds prior to baseline and during a 5.5-year follow-up with changes in adiposity markers, and the effect of sex on these associations, with adjustment for multiple confounders including the effects of depressive episodes and their severity. Data stemmed from a prospective cohort study including 2479 randomly selected 35-66 year-old residents of an urban area (mean age 49.9 years, 53.3% women) who underwent physical and psychiatric evaluations at baseline and follow-up. Weight, height, waist circumference, and body fat were measured by trained nurses and information on diagnosis and antidepressant use prior to baseline and during follow-up was collected through standardized interviews. In the fully adjusted models, the number of antidepressants, mainly SSRIs and TCAs, used prior to baseline, was associated with a lower increase of body-mass index (BMI, ß (95%CI) = -0.12 (-0.19, -0.05)) and waist circumference (ß = -0.28 (-0.56, -0.01)), whereas participants treated with antidepressants during the follow-up had a steeper increase in BMI (ß = 0.32 (0.13, 0.50)) and waist circumference (ß = 1.23 (0.44, 2.01)). Within the class of SSRIs, the use of fluoxetine, sertraline or escitalopram during follow-up was associated with a steeper increase in adiposity markers. The associations of SSRIs with BMI and waist circumference were only observed when the SSRIs were used during the second period of the follow-up. Sex did not moderate these associations. Our findings suggest an increase of adiposity markers during sustained treatment with TCAs and SSRIs, which however return to normal levels after cessation of treatment. Hence, the benefit of long-term administration of these antidepressants should be carefully weighed against the potential risk of weight gain.

Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank.

BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

Doublecortin-like knockdown in mice attenuates obesity by stimulating energy expenditure in adipose tissue.

Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, ß-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by ß-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity.

Epicardial and liver fat implications in albuminuria: a retrospective study.

BACKGROUND: Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. METHODS: A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. RESULTS: After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20-8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69-22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15-30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]). CONCLUSIONS: Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.

Epicardial fat thickness in rheumatoid arthritis: Insights from echocardiographic analysis and autoimmune correlations.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects the joints. RA is associated with high cardiovascular mortality and morbidity. One of the new markers of cardiometabolic risk is epicardial fat thickness, the study of EFT in patients with RA and its association with echocardiographic parameters may provide valuable insight into the potential cardiac involvement and overall cardiovascular risk in these patients. METHOD: The present study is a cross-sectional study with a comparison group conducted in 2024. The study population included 66 RA patients and 66 healthy participants. Echocardiographic parameters, laboratory data including lipid profile and inflammatory markers, were obtained from the medical record. RESULTS: Comparison of echocardiographic parameters between RA and healthy participants showed that E parameter and EFT were statistically significant in RA patients. (EFT was 5.22 ± 2.6 in RA patients which in comparison with healthy participant (5.22 ± 2.06) was statistically significant (p-value: <.001)). Also, EFT was correlated with RF, Anti-CCP, ESR, and systolic blood pressure. CONCLUSION: To the best of our knowledge, ours is the first EFT study on RA patients in Iran, which shows a higher EFT in RA patients. High EFT is correlated with more cardiovascular events and is an early sign and independent predictor of atherosclerosis in RA patients, which greatly underlines the importance of cardiovascular assessment in RA patients.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

The visceral adiposity index is associated with asthma, especially current asthma: A cross-sectional study of NHANES, 2003 to 2018.

To investigate the association between the visceral adiposity index (VAI) and asthma using data from National Health and Nutrition Examination Survey 2003 to 2018 by a cross-sectional study. We explored the potential relationship between the VAI and asthma incidence via a cross-sectional study of the National Health and Nutrition Examination Survey from 2003 to 2018. Multiple logistic regression analysis, restricted cubic spline analysis and subgroup analysis were performed. Among the 80,312 participants, 1984 had been told by a doctor or other health professional, and 1142 still had asthma. With all confounders controlled, the VAI was positively associated with asthma incidence (odds ratios 1.04, 95% confidence interval: 1.01, 1.08). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for asthma risk were 1.02 (0.86, 1.21), 1.14 (0.96, 1.36), and 1.18 (1, 1.39), respectively (P for trend = .02). Subgroup analysis revealed no significant interaction effect among the subgroups (P > .05). The positive association was stronger in current asthma patients (odds ratios 1.13, 95% confidence interval: 1.03, 1.24). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios for current asthma risk were 1.15 (0.81, 1.64), 1.29 (0.91, 1.84), and 1.51 (1.01, 2.24), respectively (P for trend .04). The restricted cubic spline regression analysis did not reveal a nonlinear correlation between the VAI and asthma or current asthma. Subgroup analysis revealed a significant interaction effect between age (P for interaction = .03) and diabetes status (P for interaction = .02). Except in the age ≥60 years, Less than high school, normal body mass index subgroup, VAI, and current asthma were positively correlated. A positive relationship between the VAI and asthma incidence was observed. In particular, there was a strong positive correlation between the VAI score and current asthma. According to the subgroup analysis, more attention should be given to individuals aged 40 to 59 years who have diabetes.

Exploring the effect of sedentary behavior on increased adiposity in middle-aged adults.

BACKGROUND: Sedentary behavior is linked to excess fat mass; however, this association may be inconclusive due to potential measurement errors in self-reported sedentary behavior. OBJECTIVE: To assess the association between changes in sedentary behavior and fat mass in a Cohort of Health Workers (HWCS) from 2004 to 2010. METHODS: A total of 1,285 adults participating in the Cohort of Health Workers were evaluated in 2004 and 2010. Fat mass (kg) was measured by dual X-ray absorptiometry. A self-administered questionnaire was used to estimate the sedentary behavior. Sedentary behavior was also estimated using accelerometry in a sample of 142 health workers. Accelerometry data were used to correct self-reported sedentary behavior using a generalized linear model, which included values for sleeping time, age, sex, sedentary behavior, glucose, and triglycerides. Concordance between both methods was assessed using a kappa and Bland-Altman analysis. Once sedentary behavior was corrected, the values were used to evaluate the association between changes in sedentary behavior and body fat mass using a fixed effect model in the cohort, adjusting for confounders. RESULTS: Self-reported sedentary behavior was 2.8 ± 1.8 and 2.3 ± 1.6 h/day, and body fat mass was 24.9 ± 8.1 and 26.8 ± 8.5 kg in 2004 and 2010, respectively. After applying the correction model, the self-reported sedentary behavior was 7.6 ± 1.2 and 7.5 ± 1.2 h/day in 2004 and 2010, respectively. For every hour increase in corrected sedentary behavior, there was an observed increase of 0.847 (p > 0.001) kg in body fat mass during the 6.8 years in the Cohort of Health Workers from 2004 to 2010. Conversely, non-corrected self-reported sedentary behavior was associated with a non-significant reduction of 0.097 kg (p = 0.228) for every hour of sedentary behavior. CONCLUSIONS: Increased sedentary behavior was associated with increased body fat mass when corrected self-reported sedentary behavior was used. Implementing public health strategies to reduce sedentary behavior is imperative.

Causal effect of obesity and adiposity distribution on the risk of pressure ulcers and potential mediation by type 2 diabetes mellitus: insights from multivariable mendelian randomization and mediation analysis.

Previous observational studies have identified a link between obesity, adiposity distribution, type 1 Diabetes Mellitus (T1DM), type 2 Diabetes Mellitus (T2DM), and the risk of pressure ulcers (PUs). However, the definitive causality between obesity and PUs, and potential DM mediators remains unclear. Univariable, multivariable, and mediation Mendelian randomization (MR) analyses were conducted to explore the mediating role of T1DM or T2DM in the association between obesity, adiposity distribution, and PUs. Instrumental variables for obesity and adiposity distribution, including Body Mass Index (BMI), waist circumference, hip circumference, trunk fat mass, whole body fat mass, trunk fat percentage, and body fat percentage, were selected from two genome-wide association studies (GWAS). In univariable MR analysis, BMI, hip circumference, and obesity were associated with PUs using inverse variance weighted (IVW) regression. These findings were further corroborated by the replication cohorts and meta-analysis (BMI: OR = 1.537, 95% CI = 1.294-1.824, p < 0.001; Hip circumference: OR = 1.369, 95% CI = 1.147-1.635, p < 0.001; Obesity: OR = 1.235, 95% CI = 1.067-1.431, p = 0.005), respectively. Even after adjusting for confounding factors such as T1DM and T2DM, BMI and hip circumference remained statistically significant in multivariable MR analyses. T2DM may mediate the pathogenesis of BMI-related (OR = 1.106, 95% CI = 1.054-1.160, p = 0.037) and obesity-related PUs (OR = 1.053, 95% CI = 1.034-1.973, p = 0.004). These findings provide insights for the prevention and treatment of PUs, particularly in patients with obesity or DM.

Association between visceral adiposity index and incidence of diabetic kidney disease in adults with diabetes in the United States.

Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 ± 0.18 in the DKD group and 2.76 ± 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR ≧ 3 (OR = 1.085, 95% CI 1.021, 1.160), BMI ≧ 30 kg/m2 (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations.

Association of serum 25-hydroxy vitamin D status with cardiometabolic risk factors and total and regional obesity in southern Iran: evidence from the PoCOsteo study.

Cardiometabolic risk factors increase the chance of developing cardiovascular disease (CVD) and type 2 diabetes. Most CVD risk factors are influenced by total and regional obesity. A higher risk of developing CVD may be linked to vitamin D deficiency, which is more prevalent in the older population. With the goal of evaluating the association between vitamin D and cardiometabolic risk factors and total and regional obesity in older adults, this research included 25 (OH) vitamin D3 concentrations and biochemical markers associated with cardiometabolic diseases, as well as total and regional adiposity, which was measured by DXA. A total of 1991 older participants in the PoCOsteo study were included. Overall, 38.5% of participants had vitamin D deficiency. After adjusting for confounders, the results of multiple linear and logistic regression suggested an inverse association between vitamin D and body mass index (P = 0.04), waist circumference (P = 0.001), total fat (P = 0.02), android fat (P = 0.001), visceral fat (P < 0.001), subcutaneous fat (P = 0.01), trunk fat (P = 0.006), arm fat (P = 0.03), high systolic blood pressure (P = 0.004), high total cholesterol (P < 0.001), high LDL-cholesterol (P < 0.001), high serum triglycerides (P = 0.001), and high fasting glucose (P < 0.001). Additionally, higher vitamin D concentrations decreased the risk of dyslipidemia by 2%. Our results showed a significant association between serum vitamin D and a number of cardiometabolic risk factors, including total and regional obesity.

Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner.

Sex steroids modulate the distribution of mammalian white adipose tissues. Moreover, WAT remodeling requires adipocyte progenitor cells. Nevertheless, the sex-dependent mechanisms regulating adipocyte progenitors remain undetermined. Here, we uncover Cxcr4 acting in a sexually dimorphic manner to affect a pool of proliferating cells leading to restriction of female fat mass. We find that deletion of Cxcr4 in Pparγ-expressing cells results in female, not male, lipodystrophy, which cannot be restored by high-fat diet consumption. Additionally, Cxcr4 deletion is associated with a loss of a pool of proliferating adipocyte progenitors. Cxcr4 loss is accompanied by the upregulation of estrogen receptor alpha in adipose-derived PPARγ-labelled cells related to estradiol hypersensitivity and stalled adipogenesis. Estrogen removal or administration of antiestrogens restores WAT accumulation and dynamics of adipose-derived cells in Cxcr4-deficient mice. These findings implicate Cxcr4 as a female adipogenic rheostat, which may inform strategies to target female adiposity.

Difference in Body Composition Patterns between Age Groups in Italian Individuals with Overweight and Obesity: When BMI Becomes a Misleading Tool in Nutritional Settings.

Little is known about the changes in body composition (BC) in people with overweight or obesity. The aim of this study was to assess the differences in BC patterns in this population based on gender and age. A total of 2844 Italian adults of mixed gender and a body mass index (BMI) of ≥25 kg/m2 underwent a BC assessment by means of dual-energy X-ray absorptiometry (DXA). The sample was categorized into three age groups: 'young' (20-39 years), 'middle' (40-59 years), and 'older' (60-80 years) adults, after being matched by body weight and BMI. Males showed higher total body fat percentage (BF%) and a lower total lean mass (LM), progressively from the young to the middle to the older age groups, while females showed similar values for these total compartments between the three age groups. However, in both genders, participants in the middle and older groups were more likely to have a higher trunk fat percentage by +1.23% to +4.21%, and lower appendicular lean mass (ALM) by -0.81 kg to -2.63 kg with respect to the young group, indicating expression of major central adiposity and sarcopenia. While our findings underscore the limitations of BMI to detect these differences between age groups, the identification of new tools suitable for this aim is greatly needed in this population. Moreover, further investigation that clarifies the impact of these differences in BC patterns between gender and age groups on health outcomes is also required.

Prediction of visceral adipose tissue magnitude using a new model based on simple clinical measurements.

Aims: Waist circumference (WC) is a reliable obesity surrogate but may not distinguish between visceral and subcutaneous adipose tissue. Our aim was to develop a novel sex-specific model to estimate the magnitude of visceral adipose tissue measured by computed tomography (CT-VAT). Methods: The model was initially formulated through the integration of anthropometric measurements, laboratory data, and CT-VAT within a study group (n=185), utilizing the Multivariate Adaptive Regression Splines (MARS) methodology. Subsequently, its correlation with CT-VAT was examined in an external validation group (n=50). The accuracy of the new model in estimating increased CT-VAT (>130 cm2) was compared with WC, body mass index (BMI), waist-hip ratio (WHR), visceral adiposity index (VAI), a body shape index (ABSI), lipid accumulation product (LAP), body roundness index (BRI), and metabolic score for visceral fat (METS-VF) in the study group. Additionally, the new model's accuracy in identifying metabolic syndrome was evaluated in our Metabolic Healthiness Discovery Cohort (n=430). Results: The new model comprised WC, gender, BMI, and hip circumference, providing the highest predictive accuracy in estimating increased CT-VAT in men (AUC of 0.96 ± 0.02), outperforming other indices. In women, the AUC was 0.94 ± 0.03, which was significantly higher than that of VAI, WHR, and ABSI but similar to WC, BMI, LAP, BRI, and METS-VF. It's demonstrated high ability for identifying metabolic syndrome with an AUC of 0.76 ± 0.03 (p<0.001). Conclusion: The new model is a valuable indicator of CT-VAT, especially in men, and it exhibits a strong predictive capability for identifying metabolic syndrome.

Body fat distribution and bone mineral density in a multi-ethnic sample of postmenopausal women in The Malaysian Cohort.

In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this. PURPOSE: To investigate associations of total and regional adiposity with bone mineral density (BMD) among a multi-ethnic cohort of postmenopausal women. METHODS: Dual X-ray absorptiometry (DXA) imaging was undertaken for 1990 postmenopausal women without prior chronic diseases (30% Malay, 53% Chinese, and 17% Indian) from The Malaysian Cohort (TMC). The strength of the associations between standardized total and regional body fat percentages with total and regional BMD was examined using linear regression models adjusted for age, height, lean mass, ethnicity, education, and diabetes. Effect modification was assessed for ethnicity. RESULTS: Women with a higher total body fat percentage were more likely to be Indian or Malay. Mean (SD) BMD for the whole-body total, lumbar spine, leg, and arm were 1.08 (0.11), 0.96 (0.15), 2.21 (0.22), and 1.36 (0.12) g/cm2, respectively. Total body and visceral fat percentage were inversely associated with total BMD (- 0.02 [95% CI - 0.03, - 0.01] and - 0.01 [- 0.02, - 0.006] g/cm2 per 1 SD, respectively). In contrast, subcutaneous and gynoid fat percentages were positively associated with BMD (0.007 [0.002, 0.01] and 0.01 [0.006, 0.02] g/cm2, respectively). Total body fat percentage showed a weak positive association with lumbar BMD (0.01 [0.004, 0.02]) and inverse associations with leg (- 0.04 [- 0.06, - 0.03]) and arm (- 0.02 [- 0.03, - 0.02]) BMD in the highest four quintiles. There was no effect modification by ethnicity (phetero > 0.05). CONCLUSION: Total adiposity was inversely associated with total BMD, although regional associations varied. There was no heterogeneity across ethnic groups suggesting adiposity may be a risk factor for low BMD across diverse populations.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Subscapular skinfold thickness, not other anthropometric and dual-energy X-ray absorptiometry-measured adiposity, is positively associated with the presence of age-related macular degeneration: a cross-sectional study from National Health and Nutrition Examination Survey 2005-2006.

OBJECTIVE: Current literature reveals an association between anthropometric measures of adiposity (AnthM) and age-related macular degeneration (AMD), but few have explored the disease association with imaging methods. This study aimed to explore the relationship between AMD status and dual-energy X-ray absorptiometry measures (DEXAMs) among a representative sample of the US population, and compare the association with AnthM. METHOD: Using a representative sample in the National Health and Nutrition Examination Study 2005-2006 (n=1632), DEXAMs across the whole body and waist (ie, android), and relative fat distributions (eg, percentage fat, android-to-total body ratio) were analysed between no AMD (baseline) and any AMD. Bivariate analyses across AMD status were similarly performed for AnthM (ie, body mass index, waist circumference and skinfold thicknesses) and potential confounders (ie, demographics and health-related variables). Significant adiposity measures were analysed using logistic regression, adjusting for confounders. RESULTS: The participants in the sample were aged 40-69 years, were majority female (52%) and mainly Caucasian (76.5%). Bivariate analysis revealed having any AMD had positive significant associations with android-to-total fat ratio and subscapular skinfold thickness (SSFT). Other AnthM and DEXAMs were not significant. After adjusting age, gender and prescription of cholesterol-lowering medicine, only SSFT remained significantly associated. CONCLUSION: SSFT represents an independent risk factor for AMD presence compared with other AnthM and DEXAMs. SSFT is an established method of measuring fat under the skin (ie, subcutaneous fat). Hence, subcutaneous fat may be more relevant in explaining the adiposity-AMD link due to physiological properties specific to the tissue. Limitations include the restricted age range and low numbers of participants with late AMD.

Evaluation of bone marrow glucose uptake and adiposity in male rats after diet and exercise interventions.

Objectives: Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats. Methods: Eight-week-old male Sprague-Dawley rats were fed ad libitum either HFD or chow diet for 24 weeks. Additionally after 12 weeks, HFD-fed rats switched either to chow diet, voluntary intermittent running exercise, or both for another 12 weeks. BMAd morphology was assessed by perilipin-1 immunofluorescence staining in formalin-fixed paraffin-embedded tibial sections. Insulin-stimulated sternal and humeral BMGU were measured using [18F]FDG-PET/CT. Tibial microarchitecture and mineral density were measured with microCT. Results: HFD rats had significantly higher whole-body fat percentage compared to the chow group (17% vs 13%, respectively; p = 0.004) and larger median size of BMAds in the proximal tibia (815 µm2 vs 592 µm2, respectively; p = 0.03) but not in the distal tibia. Switch to chow diet combined with running exercise normalized whole-body fat percentage (p < 0.001) but not the BMAd size. At 32 weeks of age, there was no significant difference in insulin-stimulated BMGU between the study groups. However, BMGU was significantly higher in sternum compared to humerus (p < 0.001) and higher in 8-week-old compared to 32-week-old rats (p < 0.001). BMAd size in proximal tibia correlated positively with whole-body fat percentage (r = 0.48, p = 0.005) and negatively with humeral BMGU (r = -0.63, p = 0.02). HFD significantly reduced trabecular number (p < 0.001) compared to the chow group. Switch to chow diet reversed this as the trabecular number was significantly higher (p = 0.008) than in the HFD group. Conclusion: In this study we showed that insulin-stimulated BMGU is age- and site-dependent. BMGU was not affected by the study interventions. HFD increased whole-body fat percentage and the size of BMAds in proximal tibia. Switching from HFD to a chow diet and running exercise improved glucose homeostasis and normalized the HFD-induced increase in body fat but not the hypertrophy of BMAds.

Exploring the relationship between life course adiposity and sepsis: insights from a two-sample Mendelian randomization analysis.

Objectives: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence. Methods: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates. Results: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results. Conclusion: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.

Adiposity, fat-free mass and incident heart failure in 500 000 individuals.

BACKGROUND AND AIMS: The independent role of body fat distribution and fat-free mass in heart failure (HF) risk is unclear. We investigated the role of different body composition compartments in risk of HF. METHODS: Present analyses include 428 087 participants (mean age 55.9 years, 44% male) from the UK Biobank. Associations of long-term average levels of body composition measures with incident HF were determined using adjusted Cox proportional hazards regression models. RESULTS: Over a median follow-up of 13.8 years, there were 10 455 first-ever incident HF events. Overall, HF risk was more strongly associated with central adiposity (waist circumference (WC) adjusted for body mass index (BMI); HR 1.38, 95% CI 1.32 to 1.45) than general adiposity (BMI adjusted for WC; HR 1.22, 95% CI 1.16 to 1.27). Although dual X-ray absorptiometry-derived body fat remained positively related to HF after adjustment for fat-free mass (HR 1.37, 95% CI 1.18 to 1.59), the association of fat-free mass with HF was substantially attenuated by fat mass (HR 1.12, 95% CI 1.01 to 1.26) while visceral fat (VAT) remained associated with HF independent of subcutaneous fat (HR 1.20, 95% CI 1.09 to 1.33). In analyses of HF subtypes, HF with preserved ejection fraction was independently associated with all fat measures (eg, VAT: HR 1.23, 95% CI 1.12 to 1.35; body fat: HR 1.36, 95% CI 1.17 to 1.57) while HF with reduced ejection fraction was not independently associated with fat measures (eg, VAT: HR 1.29, 95% CI 0.98 to 1.68; body fat: HR 1.29, 95% CI 0.80 to 2.07). CONCLUSIONS: This large-scale study shows that excess adiposity and fat mass are associated with higher HF risk while the association of fat-free mass with HF could be explained largely by its correlation with fat mass. The study also describes the independent relevance of body fat distribution to HF subtypes, suggesting different mechanisms may be driving their aetiopathogenesis.