Search

Objective: The association between obesity, metabolic dysregulation, and the aggressive pathological traits of papillary thyroid carcinoma (PTC) continues to be a contentious issue. To date, no investigations have examined the impact of metabolic status on the malignant pathological features of PTC in relation to obesity., Methods: This research involved 855 adult patients with PTC from Shandong Provincial Hospital, classified into 4 groups based on metabolic and obesity status: metabolically healthy nonobese, metabolically unhealthy nonobese (MUNO), metabolically healthy obese, and metabolically unhealthy obese. We employed logistic regression to investigate the relationship between these metabolic obesity phenotypes and PTC's pathological characteristics. Mediation analysis was also performed to determine metabolic abnormalities' mediating role in the nexus between obesity and these characteristics., Results: Relative to metabolically healthy nonobese individuals, the metabolically unhealthy obese group was significantly associated with an elevated risk of larger tumor sizes and a greater number of tumor foci in PTC. Mediation analysis indicated that obesity directly influences tumor size, whereas its effect on tumor multifocality is mediated through metabolic dysfunctions. Specifically, high-density lipoprotein cholesterol levels were notably associated with tumor multifocality within obese subjects, serving as a mediator in obesity's impact on this trait., Conclusion: The concurrent presence of obesity and metabolic dysregulation is often connected to more aggressive pathological features in PTC. The mediation analysis suggests obesity directly affects tumor size and indirectly influences tumor multifocality via low high-density lipoprotein cholesterol levels., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Aims: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk., Materials and Methods: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death., Results: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity., Conclusions: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them., Methods: Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self-report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator., Results: Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12-1.27), while college-educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73-0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] -0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women., Conclusions: In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aim: To determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk., Methods: 35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes., Results: After 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P < 0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; P Interaction =0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036)., Conclusions: The early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Qi, Chen, Qin, Wu, Wang, Zhao, Xu, Li, Chen, Chen, Chen, Deng, Gao, Huo, Li, Liu, Luo, Mu, Qin, Shen, Shi, Su, Wan, Wang, Wang, Wang, Hu, Xu, Yan, Yang, Yu, Zhang, Zeng, Tang, Ye, Zhao, Bi, Ning, Lu and Wang.)

Objectives: Nationwide studies focusing on the impact of early-onset type 2 diabetes and obesity on the development of cardiovascular diseases (CVD) are limited in China. We aimed to investigate the association between age at diagnosis of type 2 diabetes and the risk of CVD, and to further examine the modifying effect of obesity on this association among Chinese adults., Methods: This study included 23,961 participants with previously diagnosed diabetes from a large nationwide population-based cohort study across mainland China. With an interviewer-assisted questionnaire, we collected detailed information on CVDs. Logistic regression analysis was used to evaluate the risk of CVDs associated with age at diagnosis of diabetes., Results: Compared with patients with late-onset diabetes (≥60 years), those with earlier-onset diabetes had increased risks for CVD, with adjusted ORs (95% CIs) of 1.72 (1.36-2.17), 1.52 (1.31-1.75) and 1.33 (1.19-1.48) for patients diagnosed aged <40, 40-49 and 50-59 years, respectively. Each 5-year earlier age at diagnosis of type 2 diabetes was significantly associated with 14% increased risk of CVD (OR, 1.14; 95%CI, 1.11-1.18). This association was more prominent for patients with obesity than those with normal body mass index (BMI). Significant interaction was detected between age at diagnosis and BMI categories on CVD risk ( P for interaction=0.0457)., Conclusion: Early-onset type 2 diabetes was significantly associated with higher risk of CVD, and this association was more prominent among patients with obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Lin, Zhu, Zhang, Wang, Zhang, Qi, Li, Zhu, Huo, Wan, Qin, Hu, Shi, Su, Yu, Yan, Qin, Tang, Chen, Xu, Xu, Wang, Zhao, Gao, Wang, Shen, Luo, Chen, Li, Ye, Zhang, Liu, Wang, Yang, Deng, Chen, Zeng, Li, Zhao, Mu, Bi, Wang, Ning, Wu, Chen and Lu.)

Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2a f/f , Kdm2a -/- ) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a -/- increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a -/- mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a -/- macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a -/- mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.

Background: National investigations on the interaction of insulin resistance, β-cell dysfunction, and obesity with the development of diabetes are scarce in China. We aimed to investigate the individual and joint associations of insulin resistance and β-cell dysfunction with incident diabetes, and to examine the modifying effect of BMI and waist circumference on these associations among adults with normal glucose tolerance and with prediabetes., Methods: In this nationwide, population-based, prospective cohort study, we analysed data from the China Cardiometabolic Disease and Cancer Cohort Study, which recruited adults aged 40 years or older during 2011-12 (baseline) and invited participants to attend follow-up visits in 2014-16. Patients with diabetes at baseline, missing data for baseline measures of glucose tolerance status, missing data for baseline homoeostasis model assessment (HOMA) indexes, missing data for baseline covariates, and missing data for measures of glucose tolerance status at follow-up visits were excluded. At baseline and follow-up visits, a comprehensive set of questionnaires, clinical measurements, oral glucose tolerance tests, and laboratory examinations were carried out following standardised protocols. Glucose tolerance status and prediabetes were defined according to the American Diabetes Association 2010 criteria. In the main analysis, we examined the contributions of insulin resistance (HOMA of insulin resistance [HOMA-IR]) and β-cell dysfunction (HOMA of β-cell function [HOMA-B]) to diabetes risk, and evaluated the impact of obesity on these associations., Findings: 94 952 participants (31 517 men and 63 435 women) were included in the analysis. High HOMA-IR was associated with a greater hazard of diabetes (quartile 4 vs 1: hazard ratio [HR] 6·70, 95% CI 6·08-7·39; per unit increase in Z score: HR 2·17, 95% CI 2·10-2·24) than low HOMA-B (quartile 1 vs 4: 4·08, 3·72-4·48; per unit decrease in Z score: 1·92, 1·85-2·00). Approximately 24·4% (95% CI 23·6-25·2) of the incident diabetes could be attributed to insulin resistance and 12·4% (11·2-13·7) could be attributed to β-cell dysfunction. The HRs for diabetes were 1·83 (95% CI 1·72-1·95) per unit increase in Z score of HOMA-IR and 2·03 (1·86-2·21) per unit decrease in Z score of HOMA-B among participants with normal weight; the corresponding HRs for diabetes were 2·02 (1·93-2·11) and 1·88 (1·79-1·98) among participants with obesity (p interaction =0·0091). These associations and interactions were similar for participants with normal glucose tolerance or prediabetes., Interpretation: Insulin resistance shows a stronger association with incident diabetes than does β-cell dysfunction in Chinese adults, and this association pattern was more prominent among adults with obesity. Given the limitations of HOMA indexes as surrogate measures of insulin resistance and β-cell dysfunction, these findings should be interpreted with caution., Funding: National Natural Science Foundation of China., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes., Methods: A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis., Results: The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10-1.52; P = 0.002) or 1.12- (95% CI 1.01-1.27; P = 0.039) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively., Conclusion: Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.

In order to prevent cardiovascular endpoints, control of diabetes, hypertension and hypercholesterolemia is a necessity as those risk factors frequently occur in combination. Prevalence trends of concurrent diabetes, hypertension and hypercholesterolemia in 36,673 subjects were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999-2012. The prevalence of concurrent diabetes, hypertension and hypercholesterolemia increased from 3% in 1999-2000 to 6.3% in 2011-2012 (P < 0.001). The diabetes with concurrent hypertension or hypercholesterolemia incidences also increased significantly, while the occurrence of concurrent hypertension and hypercholesterolemia was stable over the study period. Overall medical drug treatments for concurrent diabetes, hypertension, hypercholesterolemia were improved from 69.8% in 1999-2006, to 82.4% in 2007-2012 (P = 0.002). Treatment cost coverage rates in any combinations with diabetes were 79-82.4% and 90.7% in the subgroup of concurrent hypertension and hypercholesterolemia. General treatment goal achievement rates were <25%, the lowest rate being 14.2% in the subject groups with three combined risk factors. The treatment goal achievement rates in two subgroups with concurrent diabetes were 20.1% (with hypertension) and 17% (with hypercholesterolemia) and 24.5% in the group without diabetes. Cost coverage improved in all combinations, but the general treatment goal achievement rates were low, especially in the groups with concurrent diabetes.

Background: Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk. However, the association of mildly reduced kidney function with CVD risk is unclear., Methods and Results: This study investigated the association of estimated glomerular filtration rate (eGFR) with prevalent CVDs, 10-year Framingham risk for coronary heart disease (CHD), and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) in 239 832 participants from the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study. With an interviewer-assisted questionnaire, we collected information on CVD, including reported CHD, stroke, or myocardial infarction. Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Compared with individuals with normal eGFR (≥90 mL/min per 1.73 m(2)), those with decreased eGFR (75-89, 60-74, and <60 mL/min per 1.73 m(2)) had higher risk of prevalent obesity, diabetes mellitus, hypertension, and dyslipidemia in both men and women (P for trend all <0.001). Moreover, a significantly higher 10-year Framingham risk for CHD and 10-year risk for ASCVD was observed in both men and women with mildly decreased eGFR (60-89 mL/min per 1.73 m(2))., Conclusions: Even mildly reduced eGFR (under 90 mL/min per 1.73 m(2)) is associated with elevated 10-year Framingham risk for CHD and 10-year ASCVD risk among Chinese adults., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: To clarify the quantitative relationship of body mass index (BMI) change from early adulthood to midlife with presence of type 2 diabetes mellitus (T2DM) after midlife., Methods: This study included 120,666 middle-aged and elderly, whose retrospectively self-reported body weight at 20 and 40 years and measured height were available. BMI at 20 and 40 years and BMI change in between were defined as early-adulthood BMI, midlife BMI, and early-adulthood BMI change., Results: The odds ratio (OR) for T2DM associated with an 1-unit increment of early-adulthood or midlife BMI was 1.08 (95% confidence interval (CI), 1.07-1.08) and 1.09 (95% CI, 1.09-1.10) respectively. In the cross-tabulation of both early-adulthood BMI and BMI change, the prevalence of T2DM increased across both variables. Compared with participants with normal early-adulthood weight and BMI increase/decrease ≤1, the OR (95% CI) for T2DM of participants with early-adulthood overweight/obesity and BMI increase ≥4 kg/m(2) was 3.49 (3.05-4.00). For participants with early-adulthood underweight and BMI increase/decrease ≤ 1, the OR (95% CI) was 0.85 (0.75-0.97). Subgroup analysis according to sex and age showed similar trends., Conclusions: Early-adulthood BMI may influence T2DM prevalence after midlife independent of current BMI. T2DM prevalence after midlife was positively associated with early-adulthood weight gain and inversely related to early-adulthood weight loss, while early-adulthood weight loss could not completely negate the adverse effect of early-adulthood overweight/obesity on diabetes., (© 2016 The Obesity Society.)

Background and Objectives: With an increased incidence of obesity in China, this study sought to investigate the correlation between serum 25-hydroxyvitamin D levels and adiposity phenotypes in Chinese adults from urban settings., Methods and Study Design: A total of 1277 subjects aged 20-82 years old were recruited into this cross-sectional study. Anthropometric parameters and blood biochemistry panels were measured. Statistical analysis using partial correlation, multivariable regression and covariance were performed to assess the impact of obesity parameters on serum 25-hydroxyvitamin D levels., Results: After adjustment for age and gender, serum25-hydroxyvitamin D levels were found to be inversely related to body mass index, waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat to hip fat ratio. In multivariable regression analysis, serum 25-hydroxyvitamin D levels were negatively associated with waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat/hip fat ratio (p<0.05), while there was no correlation with body mass index (p>0.05). After inclusion of body fat, body fat percentage and waist fat to hip fat ratio in one model, only waist fat to hip fat ratio remained significantly associated with serum 25-hydroxyvitamin D levels (p<0.05). The covariance analysis results showed that abdominal obesity subjects had lower serum 25-hydroxyvitamin D levels compared to the counterpart group, as defined by waist circumference or waist/hip ratio (p<0.05)., Conclusion: Our results affirm the relationship between serum 25-hydroxyvitamin D levels and abdominal obesity, suggesting that adiposity phenotypes were strongly linked to serum 25-hydroxyvitamin D levels.

Epidemiological evidence indicates that thyrotropin (TSH) is positively correlated with the severity of obesity. However, the mechanism remains unclear. Here, we show that TSH promoted triglyceride (TG) synthesis in differentiated adipocytes in a thyroid hormone-independent manner. Mice with subclinical hypothyroidism, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a 35% increase in the total white adipose mass compared with their wild-type littermates. Interestingly, Tshr KO mice, which had normal thyroid hormone levels after thyroid hormone supplementation, resisted high-fat diet-induced obesity. TSH could directly induce the activity of glycerol-3-phosphate-acyltransferase 3 (GPAT3), the rate-limiting enzyme in TG synthesis, in differentiated 3T3-L1 adipocytes. However, following either the knockdown of Tshr and PPARγ or the constitutive activation of AMPK, the changes to TSH-triggered GPAT3 activity and adipogenesis disappeared. The over-expression of PPARγ or the expression of an AMPK dominant negative mutant reversed the TSH-induced changes. Thus, TSH acted as a previously unrecognized master regulator of adipogenesis, indicating that modification of the AMPK/PPARγ/GPAT3 axis via the TSH receptor might serve as a potential therapeutic target for obesity.

Objective: Obesity and insulin resistance are risk factors for cardiovascular diseases. Whether insulin-sensitive obese individuals are at higher risk for cardiovascular diseases is still debated. We aim to investigate whether insulin-sensitive obesity associates with prevalent cardiovascular diseases and 10-year coronary heart disease (CHD) risk., Research Design and Methods: At the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, 211,641 participants aged 40 years or older were recruited from 25 communities across the China mainland, in 2011 to 2012. Participants were categorized by insulin-sensitive/resistant and general/abdominal obese status. Cardiovascular diseases included CHD, stroke, and myocardial infarction. Framingham risk score (FRS) was calculated according to National Cholesterol Education Program-Adult Treatment Panel III and FRS greater than 20% or cardiovascular diseases were identified as high risk for 10-year CHD., Results: Controlling for potential confounders, compared with insulin-sensitive normal weight individuals, insulin-sensitive general obese individuals had increased risks for prevalent cardiovascular diseases (men: OR, 2.55, 95% CI, 2.04-3.18; women: 1.73, 1.45-2.06) and 10-year Framingham risk for CHD (men: 2.26, 1.86-2.76; women: 1.73, 1.46-2.06). Compared with insulin-sensitive normal waist subgroup, insulin-sensitive abdominal obesity was associated with higher risks for prevalent cardiovascular diseases (men: 1.32, 1.20-1.46; women: 1.36, 1.27-1.47) and 10-year Framingham risk for CHD (men, 1.34, 1.23-1.45; women, 1.37, 1.27-1.47)., Conclusion: Both general and abdominal obesity were associated with elevated prevalent cardiovascular diseases and 10-year CHD risk, regardless of the presence or absence of insulin resistance., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The effects of a high protein diet on insulin secretion and glucose metabolism have been quite controversial. The aim of this study was to evaluate the effects of long-term isocaloric high animal protein intake on insulin secretion in diet-induced obese rats., Results: After the experimental period (24 weeks), the high-fat diet-induced obese rats that were fed isocaloric high-protein diets (HP) had lower body weight gain (P < 0.01) and lower visceral fat (P < 0.05) than normal protein (NP) rats. Fasting plasma glucagon-like peptide-1 (GLP-1) was also reduced significantly (P < 0.05), as well as serum insulin levels at 5 min and 10 min by intravenous insulin releasing test. In addition, insulin mRNA and pancreatic duodenal homeodomain-1 (PDX-1), GLP-1 protein expression were both markedly lower in HP rats (P < 0.05), while PDX-1 mRNA in HP rats had no difference from NP rats., Conclusion: These results suggest that long-term isocaloric high animal protein intake reduces the acute insulin response in obese rats and the decrease of insulin is associated with both reduced weight gain and inhibition of PDX-1 expression. GLP-1 might be a negative feedback for the balance of energy metabolism secondary to changes of body weight and visceral fat., (Copyright © 2012 Society of Chemical Industry.)

Background: Obesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity., Methods: In the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated., Results: We here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P < 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index)., Conclusion: Taken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: Patients with bladder cancer (BC) are at high risk for recurrence rates and readmission costs. However, the evidence about obesity and metabolic abnormalities on the BC prognosis was inconsistent. Our primary aim was to determine the impact of obesity and different metabolic status on the readmission risk in patients with BC. Design and methods: We identified 16,649 patients with BC using the 2018 Nationwide Readmissions Database who were hospitalized from January to June 2018 and followed for 180days. The primary outcome was 180-day readmission. The multivariate Cox regression analysis and ordered logistic regression were performed to analyze data. Results: Obesity and metabolic abnormalities were associated with an increased readmission risk in patients with BC [obesity: adjusted hazard ratio (aHR)=1.08, 95% confidence interval (CI): 1.01–1.16; hyperglycemia: aHR=1.11, 95% CI: 1.05–1.17; hypertension: aHR=1.09, 95% CI: 1.03–1.15]. Compared with non-obese and no metabolic abnormalities, the risk of readmission was significantly increased in patients with metabolic abnormalities, irrespective of obesity (non-obese and metabolic abnormalities: aHR=1.07, 95% CI: 1.02–1.13; obese and metabolic abnormalities: aHR=1.20, 95% CI: 1.10–1.31), but not in obese and no metabolic abnormalities. These associations were consistent in patients aged 60years or older and the surgery group. Moreover, hyperglycemia, hypertension, and a graded increment of metabolic risk were associated with an increased readmission risk. We also found increased length of stay for readmission in patients with obesity and metabolic abnormalities (aOR=1.17, 95% CI: 1.00–1.36). Conclusion: Obesity with metabolic abnormalities and metabolic abnormalities alone were associated with higher readmission risks in patients with BC. It is suggested that prevention should focus not only on obesity but also on metabolic abnormalities to decrease the risk of readmission. [ABSTRACT FROM AUTHOR]

Objective: Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity development. The preoptic area (POA) of the hypothalamus is a critical area for control of BAT thermogenesis. However, the intracellular signaling cascades in the POA for regulation of BAT thermogenesis are poorly understood.Methods: Phosphorylation proteomics (phosphoproteomics) and bioinformatics approaches were used to disclose numerous hypothalamic signaling pathways involved in the regulation of BAT thermogenesis. Conditional manipulation of the p38α gene in mouse POA was performed by stereotaxic injection of adeno-associated virus 9 vector to explore the role of p38α in BAT thermogenesis.Results: Multiple hypothalamic signaling pathways were triggered by cold exposure, especially the mitogen-activated protein kinase (MAPK) signaling pathway. The p38α activation, but not extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK), in the hypothalamus was significantly decreased during cold exposure. p38α deficiency in the POA dramatically elevated energy expenditure owing to a marked increase in BAT thermogenesis, resulting in significantly decreased body weight gain and fat mass. Overexpression of p38α in the POA led to a dramatic increase in weight gain.Conclusions: These results demonstrate that p38α in the POA exacerbates obesity development, at least in part owing to a decrease in BAT thermogenesis. [ABSTRACT FROM AUTHOR]

Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% received one or more doses of vaccine, respectively. In the UK Biobank, participants are followed from the vaccination date until October 18, 2021. We found that obesity and metabolic abnormalities (namely, hyperglycemia, hyperlipidemia, and hypertension) were modifiable factors for severe COVID-19 in vaccinated patients (all p < 0.05). When metabolic abnormalities were present, regardless of obesity, the risk of severe COVID-19 was higher than that of metabolically normal individuals (all p < 0.05). Moreover, pharmacological interventions targeting such abnormalities (namely, antihypertensive [adjusted hazard ratio (aHR) 0.64, 95% CI 0.48–0.86; p = 0.003], glucose-lowering [aHR 0.55, 95% CI 0.36–0.83; p = 0.004], and lipid-lowering treatments [aHR 0.50, 95% CI 0.37–0.68; p < 0.001]) were significantly associated with a reduced risk for this outcome. These results show that more proactive health management of patients with obesity and metabolic abnormalities is critical to reduce the incidence of severe COVID-19 after vaccination. [Display omitted] • Obesity and metabolic abnormalities are highly prevalent in patients with severe COVID-19 • Obesity and metabolic abnormalities are associated with an increased risk of severe COVID-19 • In vaccinated patients, metabolic abnormalities are risk factors for severe COVID-19 • Interventions targeting metabolic abnormalities may reduce the risk of severe COVID-19 Fan et al. show that obesity and metabolic abnormalities were modifiable risk factors for severe COVID-19 events in vaccinated patients. When metabolic abnormalities (namely, hyperglycemia, hyperlipidemia, or hypertension) were present, regardless of obesity, the risk of severe COVID-19 was higher than that of metabolically normal people. Moreover, pharmacological interventions targeting such abnormalities were significantly associated with a reduced risk for this outcome. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of digestive polyps, whereas all obesity are not created equally. The role of metabolic states in occurrence risks of polyps among individuals with varying degrees of obesity remains unknown. Our study aimed to evaluate the association between metabolic obesity phenotypes and the occurrence of digestive polyps. Data from 9,278,949 patients between 2016 and 2018 from the National Inpatient Sample (NIS) database, a nationally representative database of all discharges from US health-care hospitals, were analyzed. According to obesity phenotype, the study population was classified into four groups: metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). We calculated the incidence rates of various digestive polyps (stomach/duodenum, colon and rectum polyps) among these participants by searching the hospital records for ICD-10 diagnosis codes indicating each gastric, duodenum, colon or rectal polyps. The multiple stepwise regression analysis and further in-depth subgroup analysis were used to determine the associations between metabolic obesity phenotypes and the occurrence of digestive polyps. In the total or female population, those with the MUNO and MUO phenotypes had significantly higher prevalence of digestive polyps compared with individuals with the MHNO or MHO phenotypes (all p < 0.05) and a significant difference was not found between MUNO and MUO phenotypes (p > 0.05). Obese subjects seem to be more likely to develop stomach and duodenum polyps or colon polyps than non-obese subjects in metabolically healthy people of males (MHO vs. MHNO, p < 0.05), whereas obesity status seems to have little effect on the occurrence of digestive polyps in metabolically healthy people of females (MHO vs. MHNO, p >0.05). After adjusting for the potential confounders, the MHO, MUNO and MUO phenotypes were all risk factors for stomach and duodenum polyps (OR = 1.46, 95% CI: 1.36–1.58, p < 0.01; OR = 1.19, 95% CI: 1.14–1.25, p < 0.01; OR = 1.44, 95% CI: 1.35–1.55, p < 0.01, respectively) or colon polyps (OR = 1.28, 95% CI: 1.21–1.35, p < 0.01; OR = 1.18, 95% CI: 1.14–1.22, p < 0.01; OR = 1.46, 95% CI: 1.38–1.54, p < 0.01, respectively) compared with the MHNO phenotype，especially in menopausal female. Interestingly, we also observed in further in-depth subgroup analysis that metabolic abnormalities may have a greater impact on the occurrence of digestive polyps than obesity (all p < 0.05). Both metabolic abnormities and obesity were associated with a higher risk of digestive polyps. The effect of metabolism on digestive polyp occurrence may be stronger than that of obesity, highlighting the importance of abnormal metabolic status modification regardless of obesity status. Clinical intervention should not only focus on obesity, but also on metabolic abnormalities to decrease digestive polyp risk. [Display omitted] • Both metabolic abnormities and obesity were associated with a higher risk of digestive polyps. • The effect of metabolism on the occurrence of digestive polyps may be stronger than that of obesity. • Clinical intervention should not only focus on obesity but also on metabolic abnormalities. • Sex differences in the occurrence of digestive polyps were highlighted. [ABSTRACT FROM AUTHOR]

Obesity is a potentially modifiable factor for reducing readmissions, with heterogeneity that varies according to the metabolic status. Our objective was to examine the independent or mutual relationship between obesity and metabolic abnormalities and diabetic kidney disease (DKD)-related hospitalizations. 493,570 subjects with DKD were enrolled in the 2018 Nationwide Readmission Database (NRD, United States). The at-risk population was reclassified into refined obesity subtypes based on the body mass index (BMI) classification of metabolic abnormalities (hypertension and/or dyslipidemia) to investigate the 180 d readmission risk and hospitalization costs related to DKD. The overall readmission rate was 34.1%. Patients with metabolic abnormalities, regardless of obesity, had a significantly higher risk of readmission compared to non-obese counterparts (adjusted HR, 1.11 [95% CI, 1.07–1.14]; 1.12 [95% CI, 1.08–1.15]). Hypertension appeared to be the only metabolic factor associated with readmission among individuals with DKD. Obesity without metabolic abnormalities was independently associated with readmission (adjusted HR,1.08 [1.01,1.14]), especially among males and those >65 years (adjusted HR,1.10 [1.01–1.21]; 1.20 [1.10–1.31]). Women or those ≤65 years with metabolic abnormalities (all p <0.050) had elevated readmission rates, regardless of obesity; however, no such trend was observed in obese subjects without metabolic abnormalities (adjusted HR, 1.06 [0.98,1.16]). Additionally, obesity and metabolic abnormalities were associated with elevated hospitalization costs (all p <0.0001). Increased BMI and hypertension are positively associated with readmissions and related costs among patients with DKD, which should be considered in future studies. [ABSTRACT FROM AUTHOR]

Background and Objectives: With an increased incidence of obesity in China, this study sought to investigate the correlation between serum 25-hydroxyvitamin D levels and adiposity phenotypes in Chinese adults from urban settings.Methods and Study Design: A total of 1277 subjects aged 20-82 years old were recruited into this cross-sectional study. Anthropometric parameters and blood biochemistry panels were measured. Statistical analysis using partial correlation, multivariable regression and covariance were performed to assess the impact of obesity parameters on serum 25-hydroxyvitamin D levels.Results: After adjustment for age and gender, serum25-hydroxyvitamin D levels were found to be inversely related to body mass index, waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat to hip fat ratio. In multivariable regression analysis, serum 25-hydroxyvitamin D levels were negatively associated with waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat/hip fat ratio (p<0.05), while there was no correlation with body mass index (p>0.05). After inclusion of body fat, body fat percentage and waist fat to hip fat ratio in one model, only waist fat to hip fat ratio remained significantly associated with serum 25-hydroxyvitamin D levels (p<0.05). The covariance analysis results showed that abdominal obesity subjects had lower serum 25-hydroxyvitamin D levels compared to the counterpart group, as defined by waist circumference or waist/hip ratio (p<0.05).Conclusion: Our results affirm the relationship between serum 25-hydroxyvitamin D levels and abdominal obesity, suggesting that adiposity phenotypes were strongly linked to serum 25-hydroxyvitamin D levels. [ABSTRACT FROM AUTHOR]