Obesity-related Metabolic Abnormalities Research Articles

#1320 Differential microRNA expression profile in obesity-induced kidney disease driven by high-fat diet in mice

Abstract Background and Aims Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney dysfunction in obesity-induced kidney disease (OIKD) remain unclear. MicroRNAs (miRNAs) have been implicated in the development and progression of obesity, and several candidates have been identified as critical regulators of adipogenesis and lipid metabolism, while their dysregulation contribute to obesity-related metabolic abnormalities. The aim of the present study was to decipher the kidney microRNA (miRNA) expression profile in a mouse model of obesity-induced kidney disease characterized by systemic metabolic disturbances and kidney injury that closely resemble those observed in human disease. Method Male C57BL/6J mice were randomly divided and placed either a standard diet (STD) or a high fat diet (HFD) for 10 weeks. Serum triglycerides and total, HDL and LDL cholesterol were determined by standard clinical methods. In the kidney sections, histopathological assessments were done by using PAS and Oil-Red-O staining's. Expression of renal MCP1, TNFα, α-SMA, Fibronectin, miR-146a, miR-551b and miR-5099 was assessed by real time PCR. In order to elucidate the role of differentially expressed miRNAs, a search for target genes was done using an online computational resource DIANA-miRPath v4.0. Results High fat diet (HFD)-induced obesity led to evident structural alterations in tubular and glomerular regions of the kidney, increased renal expression of adiposity-related proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism. The miRNA sequencing analysis identified a set of 9 miRNAs differentially expressed in the kidney upon HFD feeding, with miR-5099, miR-551b-3p, miR-223-3p, miR-146a-3p and miR-21a-3p showing most significant differential expression between standard diet (STD) and HFD mice. Consistently, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that 3 validated miRNAs (miR-5099, miR-551b-3p and miR-146a-3p) modulated target genes involved in metabolic and adipocytokine pathways, fatty acid and lipid metabolism, inflammatory, senescence and profibrotic pathways. Conclusion Our results propose that differentially expressed miRNAs play pivotal roles in the intricated pathophysiology of obesity-associated kidney disease and could potentially create novel treatment strategies to counteract the deleterious effects of obesity on kidney function.

The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants.

Adiposity and adipokines are closely associated with obesity-related metabolic abnormalities, but little is known regarding whether abdominal obesity is linked to type 2 diabetes mellitus (T2DM) through circulating adiponectin levels. Thus, this large-population-based study was designed to investigate the mediating effect of adiponectin in the relationship between abdominal obesity and T2DM. A total of 232,438 adults who lived in Dongguan, Guangdong Province, China, were enrolled in the present study. The circulating adiponectin concentrations were measured using latex-enhanced immunoturbidimetric assay. The association between circulating adiponectin and other clinical parameters was detected by Spearman's correlation analysis. Restricted cubic spline (RCS) regression was also used to address the non-linearity of the relationship between waist circumference and diabetes. Mediation analyses of circulating adiponectin were conducted using linear and logistic regression. Subjects with abdominal obesity had lower levels of circulating adiponectin (P < 0.001). The circulating adiponectin value was inversely related to BMI (r = -0.370, P < 0.001), waist circumference (r = -0.361, P < 0.001), and fasting plasma glucose (r = -0.221, P < 0.001). The RCS plot showed a non-linear relation linking waist circumference with T2DM (P for non-linearity < 0.001). Patients with abdominal obesity presented 2.062 times higher odds of T2DM in comparison with those with non-abdominal obesity (odds ratio, 2.062; 95% confidence interval, 1.969-2.161) after adjusting for confounders. In the mediation analyses, the circulating adiponectin mediated the association between abdominal obesity and T2DM, with a mediation effect of 41.02% after adjustments. The above results were consistent in both men and women. The relationship between abdominal obesity and T2DM is mediated through circulating adiponectin level in adults, suggesting that circulating adiponectin might be a potential predictor for controlling the adverse progression from adiposity to T2DM.

Mitochondrial Common Deletion Level in Adipose Tissue Is Not Associated with Obesity but Is Associated with a Structural Change in Triglycerides as Revealed by FTIR Spectroscopy

Objective: Several studies have shown that mitochondrial metabolism may be disrupted if the rate of the specific 4,977 bp deletion of mitochondrial DNA (mtDNA) reaches a threshold. This study aimed to investigate the possible associations between the mtDNA4977 deletion load and obesity-related metabolic abnormalities in the adipose tissue. Methods: The study included thirty obese individuals, who underwent bariatric surgery, and twelve control subjects. mtDNA4977 deletion, adenine nucleotides, and lactate levels, which show the bioenergetic status were evaluated in visceral adipose tissues. Fourier transform infrared (FTIR) spectroscopy was used to investigate the structural variations and composition of adipose tissues in the context of deletion load. Results: There were no differences between the two groups in terms of mtDNA4977 deletion, adenine nucleotides, and lactate levels. The FTIR spectra indicated a few obesity-related alterations in adipose tissues that were not related to the mtDNA deletion load. Also, statistical analysis showed a correlation between the deletion load and a band shift of 1,744 cm⁻¹, which assigns C = O stretching of the carbonyl group of the ester group in triglycerides and other esterified fatty acids, although it is not associated with obesity. Conclusions: Our data suggest that the mtDNA4977 deletion in visceral adipose tissues of obese individuals do not have a significant impact on the bioenergetic status. However, the increased accumulation of deletion may be associated with a specific change in the ester bond, indicating structural differences in the lipids. These findings shed light on our understanding of the tissue-specific distribution of mtDNA deletions and obesity-related adipose tissue pathogeneses.

Vanadium, cobalt, zinc, and rubidium are associated with markers of inflammation and oxidative stress in a Greek population with obesity.

The prevalence of obesity is rising globally, with negative effects on the socioeconomic system. As a result of its drivers which include low-grade chronic inflammation, oxidative stress, and fatty acid metabolism, this phenotype develops metabolic anomalies that exacerbate its pathogenesis. It has been discovered that metals and metalloids have substantial effects on both the immune system and metabolism and are influenced by factors connected to obesity. Although there is a known connection between metals, obesity, and related metabolic disorders, it is still under research. We determined the plasma levels of 16 metals and metalloids in 76 individuals with obesity and investigated the relationships with inflammatory and oxidative stress biomarkers in order to clarify the processes by which metals/metalloids exhibit their effects. After adjusting for age, gender, BMI, physical activity level, smoking, the existence of metabolic abnormalities, and dietary intake of the corresponding metal, regression analysis revealed the following statistically significant associations; vanadium was negatively associated with oxLDL (Beta ± SE= -0.014 ± 0.005, p=0.007), zinc was negatively associated with leptin (Beta ± SE= -12.390 ± 5.226, p=0.025), cobalt was associated negatively with adiponectin (Beta ± SE= -0.030 ± 0.012, p=0.001) and positively with MPO (Beta ± SE= 0.002 ± 0.001, p=0.023), and rubidium was negatively associated with oxLDL (Beta ± SE= -1.139 ± 0.411, p=0.008) and positively with MPO (Beta ± SE= 0.324 ± 0.102, p=0.003). The aforementioned associations highlight the need for further research, demonstrating the importance of inflammation and oxidative stress in the association between metals/metalloids and obesity-related metabolic abnormalities.

Adipose tissue macrophages as potential targets for obesity and metabolic diseases.

Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.

Abstract P112: Association of Obesity Sub-Phenotypes With Indices of Cardiac Remodeling in the Framingham Heart Study

Introduction: Many studies have reported that obesity-related metabolic abnormalities (such as diabetes and hypertension) lead to myocardial dysfunction and adverse cardiac remodeling. However, it is challenging to disentangle the effects of obesity from those of its associated metabolic comorbidities. Comparing metabolically healthy adults across different body mass index (BMI) categories can help delineate the independent effect of obesity on cardiac remodeling from the impact of metabolic comorbidities. Hypothesis: We hypothesized that metabolically healthy overweight (MHOW) and obese (MHO) participants will manifest echocardiographic measures consistent with adverse cardiac remodeling relative to their metabolically healthy counterparts with a normal BMI. Methods: A total of 6,639 participants of the Framingham Heart Study (mean age of 49 years, 55% women) underwent routine physical examinations and echocardiography. Participants who had prevalent cardiovascular disease were excluded. Individuals were classified into obesity sub-phenotypes based on their metabolic health (metabolically healthy or metabolic unhealthy) and BMI categories (normal weight, overweight, or obese). Obesity sub-phenotypes were related to echocardiographic measures using multivariable regression models adjusting for age, sex, smoking, resting systolic blood pressure (BP), resting diastolic BP, and resting heart rate. Results: Compared to metabolically healthy normal weight, MHOW and MHO were associated with increased left ventricular mass (LVM), left atrium end-systolic dimension (LAD), global longitudinal strain (GLS), and the ratio of early trans-mitral flow velocity to early diastolic mitral annulus velocity (E/e’) ( Table ). Conclusions: Evidence of adverse cardiac remodeling was seen in individuals with increasing BMI regardless of metabolic health classification. These findings indicate that MHOW and MHO states are associated with adverse cardiac remodeling.

Fermented Foods in the Management of Obesity: Mechanisms of Action and Future Challenges.

Fermented foods are part of the staple diet in many different countries and populations and contain various probiotic microorganisms and non-digestible prebiotics. Fermentation is the process of breaking down sugars by bacteria and yeast species; it not only enhances food preservation but can also increase the number of beneficial gut bacteria. Regular consumption of fermented foods has been associated with a variety of health benefits (although some health risks also exist), including improved digestion, enhanced immunity, and greater weight loss, suggesting that fermented foods have the potential to help in the design of effective nutritional therapeutic approaches for obesity. In this article, we provide a comprehensive overview of the health effects of fermented foods and the corresponding mechanisms of action in obesity and obesity-related metabolic abnormalities.

Ablation of miRNA-22 protects against obesity-induced adipocyte senescence and ameliorates metabolic disorders in middle-aged mice

High-fat diet (HFD) promotes obesity-related metabolic complications by activating cellular senescence in white adipose tissue (WAT). Growing evidence supports the importance of microRNA-22 (miR-22) in metabolic disorders and cellular senescence. Recently, we showed that miR-22 deletion attenuates obesity-related metabolic abnormalities. However, whether miR-22 mediates HFD-induced cellular senescence of WAT remains unknown. Here, we uncovered that obese mice displayed increased pri-miR-22 levels and cellular senescence in WAT. However, miR-22 ablation protected mice against HFD-induced WAT senescence. In addition, in vitro studies showed that miR-22 deletion prevented preadipocyte senescence in response to Doxorubicin (Doxo). Loss-of-function studies in vitro and in vivo revealed that miR-22 increases H2ax mRNA and γH2ax levels in preadipocytes and WAT without inducing DNA damage. Intriguingly, miR-22 ablation prevented HFD-induced increase in γH2ax levels and DNA damage in WAT. Similarly, miR-22 deletion prevented Doxo-induced increase in γH2ax levels in preadipocytes. Adipose miR-22 levels were enhanced in middle-aged mice fed a HFD than those found in young mice. Furthermore, miR-22 deletion attenuated fat mass gain and glucose imbalance induced by HFD in middle-aged mice. Overall, our findings indicate that miR-22 is a key regulator of obesity-induced WAT senescence and metabolic disorders in middle-aged mice.

Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women

BackgroundAnimal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity.MethodsThis study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m 2] and women with normal-weight (n = 22) (BMI < 25 kg/m 2). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight.ResultsIt was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non‐obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (β = − 0.448, P-value = 0.003) and SOCS3 (β = 0.465, P-value = 0.002) in SAT of all participants.ConclusionsOur findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.

The HIF1α polymorphism rs2301104 is associated with obesity and obesity-related cytokines in Han Chinese population.

To evaluate the association between genetic polymorphisms of HIF1α and obesity and obesity-related cytokines in the Han Chinese population. The study consisted of 160 subjects with obesity and 166 age- and gender-matched healthy controls. We genotyped three tag single nucleotide polymorphisms (SNPs) of HIF1α by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping technology. Plasma cytokine concentrations were determined on the Luminex platform. The genetic associations were analysed statistically. Obese subjects had significant obesity-related metabolic abnormalities, including hyperglycaemia, insulin resistance, and abnormalities in blood lipids, liver enzymes, and uric acid levels. SNP analysis of HIF1α revealed that the allele and genotype frequencies of rs2301104 were significantly associated with obesity. Our results suggest that the minor allele C of rs2301104 might be a protective mutation of obesity, and CC/CG genotypes of rs2301104 could be protective genotype of obesity. We also found that subjects with CC/CG genotypes of rs2301104 had significantly lower levels of IL-6, TNF-α, IL-1β, IL-8, and IL-10 than subjects with GG genotypes. This is the first study to report an association between HIF1α polymorphisms and obesity and obesity-related cytokines in a Han Chinese population. These results require replication in larger populations but suggest that HIF1α may play an important role in obesity development.

The New Markers of Early Obesity-Related Organ and Metabolic Abnormalities.

The objective of our study was to identify new markers related to excessive body adiposity and its early consequences. For this purpose we determined serum FGF-19 and FGF-21 concentrations in obese rats, whose role in the pathogenesis of obesity is not yet established. In addition, a total reflection X-ray fluorescence technique was applied to determine the elemental chemistry of certain tissues affected by obesity. Next, the new biochemical and molecular parameters were correlated with well-known obesity-related markers of metabolic abnormalities. Our obese rats were characterized by increased calorie consumption and body adiposity, hypercholesterolemia, elevated levels of liver enzymes and FGF-21, while the level of FGF-19 was reduced. Strong relationships between new hormones and established metabolic parameters were observed. Furthermore, we demonstrated that obesity had the greatest effect on elemental composition in the adipose tissue and liver and that rubidium (Rb) had the highest importance in distinguishing the studied groups of animals. Tissue Rb strongly correlated with both well-known and new markers of obesity. In conclusion, we confirmed serum FGF-19 and FGF-21 as useful new markers of obesity-related metabolic alternations and we robustly propose Rb as a novel indicator of excessive body adiposity and its early consequences. However, further investigations are encouraged to address this clinical issue.

Differences of Regional Fat Distribution Measured by Magnetic Resonance Imaging According to Obese Phenotype in Koreans.

Background: Obesity is commonly associated with a high risk of metabolic disorders, and obesity-related metabolic abnormalities are affected by some specific obesity phenotypes, regional fat distribution, and body mass index. However, few studies have investigated the relationship between obesity phenotypes and regional fat distribution in Korean subjects. This study aimed to assess regional fat distribution by gender using magnetic resonance imaging (MRI), and to identify a link between fat distribution and metabolic disorders in Korean subjects. Methods: This study included 35 Korean subjects (20 women, 15 men) who were classified into two groups by gender, and further divided into two groups based on their obesity phenotype: a metabolically abnormal obesity (MAO) and metabolically healthy obesity (MHO) group. Fat distribution was measured using MRI. The blood parameters were measured using a commercially available kit. Results: Women in the MAO group had more risk factors for metabolic abnormalities than those in the MHO group. Serum glucose, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels were also significantly higher in women with MAO than in those with MHO. The intermuscular adipose tissue (IMAT) of women with MAO was significantly higher than that of women with MHO. Serum HDL-C level was negatively correlated with IMAT, whereas leptin showed a positive correlation with IMAT in all subjects. Conclusions: Metabolic abnormalities according to obesity phenotype posed a higher risk in women than that in men. These findings suggest that an understanding of gender differences in relation to the association between obesity and metabolic risk would be helpful to reduce the prevalence of obesity.

1429-P: Metabolically Healthy Obese Is Actually Not Healthy but at Risk for Developing Diabetes Mellitus

Objectives: Although obese individuals without obesity related metabolic abnormalities are often defined as metabolically healthy, risks for developing such abnormalities have not been evaluated well. Recently, a prospective study showed that metabolically healthy obese subjects were at higher risk of diabetes, stroke and cardiovascular disease than metabolically healthy subjects without obesity in UK. We here analyzed the association between metabolically healthy obesity and a risk for developing diabetes in a Japanese population. Research Design and Methods: The participants were recruited from Iwaki study, a health promotion study of Japanese people aimed to prevent lifestyle-related disease. Among 1167 participants of Iwaki study held in 2014, 931 individuals attended at least one time in 2015 to 2019. We excluded 7 and 75 individuals without complete data sets and who were diagnosed with diabetes in 2014 respectively, thus 849 subjects were enrolled in this study. Obesity was defined as BMI &amp;gt;25 kg/m2. We used the National Cholesterol Education Program ATP III Guideline to categorize metabolically unhealthy as participants meeting at least two criteria of metabolic abnormalities. Results: In 2014, the number of metabolically healthy subjects without and with obesity were 6 and 1 respectively. Cox proportional hazard model showed metabolically healthy subjects with obesity were at higher risk of diabetes compared with those without obesity (Hazard ratio 3.70, p=0.002) , even if after adjusted by age and sex (Hazard ratio 3.32, p=0.005) . Conclusions: Our analysis suggest an importance of encouraging people with obesity to reduce body weight even though they are metabolically healthy. We are extending such analyses in association with other lifestyle-related diseases. Disclosure S.Mizushiri: None. M.Daimon: None. A.Kamba: None. M.Murabayashi: None. Y.Nishiya: None. R.Ito: None. A.Tamura: None. S.Ono: None. K.Matsuki: None.

Suppression of ABHD6 Promotes Healthy Expansion of Adipose Tissue in Obesity

The mode of white adipose tissue (WAT) expansion in response to positive energy balance greatly impacts obesity-related metabolic abnormalities. Pathologic WAT remodeling is characterized by reduced adipocyte differentiation capacity, chronic inflammation, ectopic fat accumulation and insulin resistance. Pan-deletion of the monoacylglycerol lipase alpha/beta hydrolase domain-6 (ABHD6) demonstrated the therapeutic potential of ABHD6 inhibitors against obesity and type 2 diabetes. However, the role of ABHD6 in diet-induced adipogenesis and adipose inflammation remains unexplored.

Cardiovascular events in metabolically healthy obese. A nationwide cohort study

Abstract Background Obesity is a risk factor for cardiovascular disease (CVD) and has been increasing globally over the past 40 years in many countries worldwide. Metabolic abnormalities such as hypertension, dyslipidemia and diabetes mellitus are commonly associated and may mediate some of the deleterious effects of obesity. A subset of obese individuals without obesity-related metabolic abnormalities may be classified as being “metabolically healthy obese” (MHO). We aimed to evaluate the associations among MHO individuals and different types of incident cardiovascular events in a contemporary population at a nationwide level. Methods From the national hospitalization discharge database, all patients discharged from French hospitals in 2013 with at least 5 years or follow-up and without a history of major adverse cardiovascular event (myocardial infarction, heart failure [HF], ischemic stroke or cardiovascular death, MACE-HF) or underweight/ malnutrition were identified. They were categorized by phenotypes defined by obesity and 3 metabolic abnormalities (diabetes mellitus, hypertension, and hyperlipidemia). In total, 2,953,816 individuals were included in the analysis, among whom 272,838 (9.5%) were obese. We evaluated incidence rates and hazard ratios for MACE-HF, cardiovascular death, myocardial infarction, ischemic stroke, new-onset HF and new-onset atrial fibrillation (AF). Adjustments were made on age, sex and smoking status at baseline. Results During a mean follow-up of 4.9 years, obese individuals with no metabolic abnormalities had a higher risk of MACE-HF (multivariate-adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI]: 1.19–1.24), new-onset HF (HR 1.34, 95% CI 1.31–1.37), and AF (HR 1.33, 95% CI 1.30–1.37) compared with non-obese individuals with 0 metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87–0.98), ischemic stroke (HR 0.93, 95% CI 0.88–0.98) and cardiovascular death (HR 0.99, 95% CI 0.93–1.04). In the models fully adjusted on all baseline characteristics, obesity was independently associated with a higher risk of MACE-HF events (HR 1.13, 95% CI 1.12–1.14), of new-onset HF (HR 1.19, 95% CI 1.18–1.20) and new-onset AF (HR 1.29, 95% CI 1.28–1.31). This was not the case for the association of obesity with cardiovascular death (HR 0.96, 95% CI 0.94–0.98), myocardial infarction (HR 0.93, 95% CI 0.91–0.95) and ischemic stroke (HR 0.93, 95% CI 0.91–0.96). Conclusions Metabolically healthy obese individuals do not have a higher risk of myocardial infarction, ischemic stroke or cardiovascular death than metabolically healthy non-obese individuals. By contrast they have a higher risk of new-onset HF and new onset AF. Even individuals who are non-obese can have metabolic abnormalities and be at high risk of cardiovascular disease events. Our observations suggest that specific studies investigating different aggressive preventive measures in specific subgroups of patients are warranted. Funding Acknowledgement Type of funding sources: None.

Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

BackgroundParental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring.MethodsThis longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model.ResultsIn male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring.ConclusionExcept for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

Unlocking the causal link of metabolically different adiposity subtypes with brain volumes and the risks of dementia and stroke: A Mendelian randomization study

To establish causal evidence for the association of adiposity-related metabolic abnormalities with brain volumes, and the risks of dementia and stroke, we applied 1- and 2-sample Mendelian randomization (MR) analyses using up to 336,309 UK Biobank participants. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral and favorable). We validated the instruments using anthropometric and cardio-metabolic traits. Both metabolically unfavorable and metabolically neutral adiposity associated with lower gray matter volume (GMV, −9.28 cm3, −12.90 to −5.66 and −12.02 cm3, −20.07 to −3.97, respectively). Metabolically favorable adiposity was tentatively associated with a higher GMV (16.21 cm3, −0.21 to 32.68). No causal evidence was seen for white matter and hippocampal volume, and volume of white matter hyperintensities, or with the risks of dementia and stroke (all p > 0.60). These findings suggest that obesity-related metabolic abnormalities may contribute to GMV atrophy, warranting further studies.

Neck Circumference is an Effective Supplement for Nonalcoholic Fatty Liver Disease Screening in a Community-Based Population.

Background Accumulating evidence has shown that neck circumference (NC) is associated with obesity-related metabolic abnormalities. Nonalcoholic fatty liver disease (NAFLD) is regarded as a liver manifestation of metabolic syndrome. This study aimed to investigate the relationship between NC and liver fat content (LFC) and NAFLD. Methods A total of 1698 subjects (577 men and 1121 women) from the Shanghai community were enrolled. All the subjects underwent NC measurement and biochemical measurements. LFC was calculated using the parameters from abdominal ultrasound images. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. Results Subjects with NAFLD based on the LFC measurement had higher values of NC, liver enzyme profiles, homoeostasis model assessment-insulin resistance index, and LFC than those without NAFLD (all P < 0.05), irrespective of sex. NC showed an upward trend with the increase of LFC in both men and women (both P < 0.05). An elevated NC could identify 55.22% of men and 50.29% of women with NAFLD based on quantitative ultrasonography. The positive correlation between NC and LFC remained significant even after adjustment for central obesity (both P < 0.05). After adjusting for confounding factors, the risk of NAFLD in subjects with an elevated NC was 1.52-fold higher in men (P=0.036) and 2.31-fold higher in women (P < 0.001). Conclusions There was a significant and positive correlation between NC and LFC. The risk of NAFLD increased significantly in subjects with an elevated NC.

Low molecular weight chitosan oligosaccharides (LMW-COSs) prevent obesity-related metabolic abnormalities in association with the modification of gut microbiota in high-fat diet (HFD)-fed mice.

In this study, the two enzymatic low molecular weight chitosan oligosaccharides (LMW-COSs), LMW-COS-H and LMW-COS-L, were prepared with average MWs of 879.6 Da and 360.9 Da, respectively. Compared to LMW-COS-L, the LMW-COS-H was more effective in improving high-fat diet (HFD)-induced metabolic abnormalities, such as obesity, hyperlipidemia, low-grade inflammation and insulin resistance. The subsequent analysis of gut microbiota showed that the supplement of LMW-COSs caused overall structural and genus/species-specific changes in the gut microbiota, which were significantly correlated with the metabolic parameters. Specifically, both of the LMW-COSs significantly decreased the relative abundance of inflammatory bacteria such as Erysipelatoclostridium and Alistipes, whereas that of the beneficial intestinal bacteria (such as Akkermansia and Gammaproteobacteria) increased significantly. This study suggested that there were potential prebiotic functions of LMW-COSs in HFD fed mice, which regulated the dysfunctional gut microbiota, alleviated low-grade inflammation and maintained the intestinal epithelial barrier.

Unsaturated alginate oligosaccharides attenuated obesity-related metabolic abnormalities by modulating gut microbiota in high-fat-diet mice.

Gut microbiota plays an important role in the high-fat diet (HFD)-induced obesity and related metabolic syndrome (MetS). Our previous study has demonstrated that unsaturated alginate oligosaccharides (UAOS) degraded by alginate lyase possess significant anti-obesity effects in HFD-fed mice. Herein, we further established that UAOS could significantly ameliorate obesity-related metabolic abnormalities, including hyperlipidemia, insulin resistance and low-grade inflammation. Particularly, the beneficial effect of UAOS on these metabolic abnormalities could be significantly reversed by antibiotic supplementation. Subsequently, the microbiological analysis has revealed that UAOS treatment can modulate the overall composition of the gut microbiota, which is highly associated with metabolic parameters. UAOS supplementation can partially reverse the gut dysbiosis induced by HFD-diet or antibiotics. Specifically, UAOS treatment selectively increased the relative abundance of beneficial intestinal bacteria (e.g. Lactobacillus and Akkermansia genus) and decreased the abundance of inflammogenic bacteria (e.g. Bacteroides and Parabacteroides). These results suggest that UAOS can attenuate the HFD-induced obesity and related abnormalities through modulating gut microbiota, indicating that UAOS can act as potent prebiotic agents in treating obesity and related metabolic diseases.