Obesity Comorbidities Research Articles

Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Risk Scores for Five Early Life Domains and Odds of Obesity and Hypertension Comorbidity

Abstract Background For outcomes such as obesity and hypertension, determinants are likely to be complex and multidimensional. Therefore, to design realistic interventions, epidemiological research should incorporate information from multiple risk exposure domains to assess the effect on health. In this paper we explore risk scores for five early life domains and odds of obesity and hypertension comorbidity. Methods We used data from 17,196 participants in the 1970 British Cohort Study. The outcome was obesity (BMI of ≥ 30) and hypertension (blood pressure&amp;gt;140/90mm Hg or self-reported doctor’s diagnosis) comorbidity at age 46. Early life domains included: ‘prenatal, antenatal, neonatal and birth’, ‘developmental attributes and behaviour’, ‘child education and academic ability’, ‘socioeconomic factors’ and ‘parental and family environment’. Stepwise backward elimination selected variables for inclusion for each domain. Predicted risk scores of obesity and hypertension for each cohort member within each domain were calculated. Logistic regression investigated the association between domain-specific risk scores and odds of obesity-hypertension, controlling for demographic factors and other domains. Results In unadjusted models, higher domain-specific risk scores were associated with increased odds of obesity-hypertension comorbidity. In adjusted analyses, higher domain-specific risk scores remained associated with increased odds of obesity-hypertension comorbidity, with the strongest associations to the parental and family environment domain (OR1.11 95%CI 1.05-1.18) and the socioeconomic factors domain (OR1.11 95%CI 1.05-1.17). Conclusions Appropriate modelling choices of combined effects of early-life risk factors need to be explored and tested. Targeted prevention interventions aimed at population groups with shared early-life characteristics could have an impact on cardiovascular risk in adulthood. Key messages • Targeted prevention interventions aimed at population groups with shared early-life characteristics could have an impact on obesity-hypertension prevalence. • Appropriate modelling choices of combined effects of early-life risk factors need to be explored and tested.

Addressing rural health disparities by optimizing “high-touch” intervention components in digital obesity treatment: The iREACH Rural study

BackgroundRural residents are more impacted by obesity and related comorbidities than their urban counterparts. Digital weight management interventions may produce meaningful weight loss among rural residents. ObjectivesThe iREACH Rural Study aims to identify “high-touch” component(s) that contribute to meaningful weight loss (≥1.5 kg) at 6-months, over and above what the 24-week core online program produces. Three treatment components are assessed: group video sessions (yes/no); self-monitoring feedback (counselor-crafted/pre-scripted, modular); and individual coaching calls (yes/no). DesignThe iREACH Rural Study is a factorial experiment (n = 616). MethodsParticipants receive up to 3 “high-touch” components (weekly synchronous facilitated group video sessions, weekly counselor-crafted self-monitoring feedback, and individual coaching calls) to determine which contribute meaningfully to 6-month weight loss. Participants complete assessments at baseline, 2 months, 6 months, and 12 months. Weight loss at 6 months (primary outcome) and 12 months (secondary outcome) is measured by Bluetooth-enabled scales. The study seeks to identify the weight loss approach for underserved rural residents which optimizes weight change outcomes and also examines costs associated with delivering different treatment constellations. SummaryThe iREACH Rural Study is the first of its kind to isolate digital weight loss intervention components to determine which meaningfully contribute to long-term weight loss among rural residing individuals. The results may be used to refine digital weight loss programs by enhancing their effectiveness to allow broad dissemination.

Adipocyte-Targeted Nanotechnology and Cell-Based Therapy for Obesity Treatment.

Obesity is a critical risk factor for the development of metabolic diseases and is often associated with dysfunctional adipocytes. Prevalent treatments such as lifestyle intervention, pharmacotherapy, and bariatric surgery are often accompanied by adverse side effects and poor patient compliance. Nanotechnology and cell-based therapy offer innovative approaches for targeted obesity treatments, as they can directly target adipocytes, regulate lipid metabolism, and minimize off-target effects. Here, we provide an overview of the intricate relationship between adipocytes and obesity, highlighting the potential of nanotechnology and cell-based therapy in obesity treatment. Additionally, we discuss the advancements of adipose-derived mesenchymal stem cells (ADMSCs) in obesity progression, including the latest challenges and considerations for developing adipose-targeted treatments for obesity. The objective is to provide a perspective on the design and development of nanotechnology and cell-based therapy for treating obesity and related comorbidities.

7279 Survodutide and Semaglutide Both Induce Weight Loss but Show Different Effects on Food Preference and Dyslipidemia in the Free Choice Diet-induced Obese Hamster Model

Abstract Disclosure: F. Briand: Employee; Self; Physiogenix. R. Augustin: Employee; Self; Boehringer Ingelheim. K. Bleymehl: Employee; Self; Boehringer Ingelheim. T. Zimmermann: Employee; Self; Boehringer Ingelheim. T. Klöckener: Employee; Self; Boehringer Ingelheim. T. Klein: Employee; Self; Boehringer Ingelheim. Introduction: Semaglutide, a GLP-1 receptor agonist, and survodutide, a GCGR/GLP-1R dual agonist, have demonstrated significant weight loss in patients with obesity. To test whether this weight loss is associated with changes in food preference and improvement in dyslipidemia, we evaluated semaglutide and survodutide in the free choice diet-induced obese and dyslipidemic hamster, a model with a human-like lipoprotein metabolism. Methods: Obesity and dyslipidemia were induced with a 20-week free choice diet, which presents hamsters with a choice between control chow diet or high fat/cholesterol diet, and normal water or 10% fructose water. Obese hamsters were then kept on this free choice diet and treated subcutaneously once daily with vehicle, semaglutide 15 nmol/kg or survodutide 15 nmol/kg for 5 weeks. Results: Compared with vehicle, semaglutide and survodutide led to a 17% and 11% body weight reduction, respectively (both p&amp;lt;0.001 vs vehicle). Compared to vehicle, both chow diet and high fat diet intakes were significantly lower during the first week of semaglutide treatment, but then returned to baseline values. However, semaglutide significantly increased normal water intake and reduced fructose-enriched water intake during the whole treatment period (both p&amp;lt;0.001). Survodutide had a different effect, as it did not alter chow diet and normal water intakes, but significantly reduced high fat diet and fructose-enriched water intakes during the 5-week treatment period. Semaglutide and survodutide significantly reduced plasma insulin levels and the HOMA-IR index of insulin resistance (both p&amp;lt;0.01 vs. vehicle). Both semaglutide and survodutide significantly reduced plasma total cholesterol levels by 24% and 41%, respectively (both p&amp;lt;0.001). This hypocholesterolemic effect led to lower HDL-cholesterol levels (-25%, p&amp;lt;0.001) but unchanged LDL-cholesterol levels for hamsters treated with semaglutide. In contrast, in hamsters treated with survodutide, cholesterol lowering was observed in all lipoprotein fractions, including LDL-cholesterol (-39%, p&amp;lt;0.001). Conclusion: Semaglutide and survodutide both induce weight loss and lower HOMA-IR, but have different effects on food preference and dyslipidemia in the obese hamster model; such effects may be attributed to the GCGR agonism of survodutide. These preclinical data highlight the potential metabolic benefits of the GCGR/GLP-1R dual agonist survodutide for the treatment of obesity and related metabolic comorbidities. Presentation: 6/3/2024

Exercise as a promoter of neurocognitive improvement in people with psychiatric disorders and comorbid obesity: a randomized controlled trial

IntroductionThe psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity (OB). MethodsPatients with major depressive disorder, bipolar disorder and, schizophrenia and with comorbid OB (n=29) received brief healthy lifestyle counseling and were randomized into two groups: guided physical activity group (GPAG) (n=10) which included 12 weeks of guided-exercise of moderate intensity and frequency, and incentive of autonomous physical activity proposals by the specialist. Standard physical activity group (SPAG) (n=19) continue with their usual daily physical activity, without guidance or incentives, over 12 weeks. Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms, and metabolic activity, as well as neurocognitive and functional performance were assessed twice, before and after intervention. Mixed one-way analysis of variance and linear regression analyses were performed. ResultsIndividuals in GPAG showed better neurocognitive and functional performance than individuals in SPAG after physical activity training (p<0.05; η²p=0.14 to 0.15). A significant improvement in cognition before and after the physical activity training in the GPAG group was found (p<0.0001; η²p=0.29). In all cases, the effect size was from moderate to large. Inflammatory activity (interleukin [IL-6]), oxidative (mitochondrial reactive oxygen species [mROS] and mitochondrial membrane potential [ΔΨm]) and inter cellular adhesion molecule 1 [ICAM1], leukocyte-endothelium adhesion [LEPMN], and p-selectin [PSEL]) levels, and cardio-metabolic (low-density lipoprotein [LDL], systolic blood pressure [SBP], and insulin) processes were significant predicting neurocognitive improve of individuals with psychiatric disorders and comorbid OB. ConclusionsPhysical activity programs may have positive impact on neurocognitive and functional performance in individuals with psychiatric disorders and OB. Exercise influences inflammatory, oxidative, vascular, and cardio-metabolic pathways, and modulate cognition. These findings may have a potential translational utility for early intervention in these disorders.

Epidemiology and comorbidities of obesity in oran, Algeria

Epidemiology and comorbidities of obesity in oran, Algeria

Chemogenetic targeting TRPV1 in obesity-induced depression: Unveiling therapeutic potential of eicosapentaenoic acid and acupuncture

The comorbidity of obesity and depression has major public health impacts, highlighting the need to understand their shared mechanisms. This study explored the connection between obesity and depression through the transient receptor potential V1 (TRPV1) signaling pathway, using obese/depressed murine models and clinical data. Mice fed a high-fat diet showed altered TRPV1 pathway expression in brain regions of the mice: downregulated in the medial prefrontal cortex (mPFC) and hippocampus, and upregulated in the hypothalamus and amygdala, influencing depression-like behaviors and inflammation. Treatments like eicosapentaenoic acid (EPA) and acupoint catgut embedding (ACE) reversed these effects, similar to observations in Trpv1−/− mice. Furthermore, chemogenetic activation in the ventral mPFC also alleviated depression via TRPV1. In our clinical validation, single nucleotide polymorphisms (SNPs) in TRPV1-related genes (PIK3C2A and PRKCA) were linked to interferon-induced depression. These findings underscore the potential of targeting TRPV1 as a therapeutic approach for obesity-related depression.

Comorbidities of Obesity in a Rural African Population Residing in Limpopo Province, South Africa: A Comparison between General and Central Obesity

Comorbidities of Obesity in a Rural African Population Residing in Limpopo Province, South Africa: A Comparison between General and Central Obesity

Obesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches.

Though obesity-related asthma associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and glucagon-like-peptide 1 (GLP-1) receptor agonists, have been associated with improved asthma outcomes, though GLP-1R agonist data in asthma is limited to individuals with co-morbid obesity. Monoclonal antibodies approved for treatment of moderate to severe asthma generally appear to be effective in individuals with obesity, though this is based on retrospective or secondary analysis of clinical trials; moreover, while most of these asthma biologics are approved for use in the pediatric population, the impact of obesity on their efficacy has not been well studied in youth. Potential therapeutic targets being investigated include IL-6, arginine metabolites, nitro-fatty acids, and mitochondrial antioxidants, with clinical trials for each currently underway. Potential therapeutic targets include adipose tissue eosinophils and the GLP-1-Arginine-Advanced glycation end products axis, though data in humans is still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of interferon-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, in order to facilitate effective treatment development for this unique asthma phenotype.

Abstract B150: Social determinants of health and comorbidities increasing inflammation cytokines related to breast cancer in African American and Latinx women

Abstract Introduction: Comorbidities such as obesity, Type-2 diabetes (T2D), and hypertension (HTN) are highly prevalent among under-resourced African Americans (AA) and Latinx, and they are associated with breast cancer (BC) risks and outcomes. Social determinants of health (SDOH) also have been found related to BC incidence, stage, and survival. In addition, elevated inflammatory cytokines may be an underlying factor in comorbidities that contribute to tumorigenesis and adverse cancer outcomes. Limited research has been conducted to explore the process and associations among SDOH, comorbidities, and inflammation cytokines related to BC. The purpose of this study was to fill this research gap using a sample recruited from AA and Latinx communities. Methods: This was a cross-sectional study conducted in South LA. A total of 570 AA and Latinx women with or without BC were recruited. A panel of 19 cytokines from serum samples were measured by Luminex assay. Demographic information, body mass index, comorbidities, and diagnosis/stage of BC were collected from patients’ medical records. SDOH factors were selected from the social vulnerability index (e.g., percentage of persons in poverty, unemployed, with no high school diploma) obtained through Geographic Information Systems. Chi-square tests, independent sample Mann-Whitney U tests, and Cox regression were employed to examine the associations between BC diagnosis/stages, comorbidities, and cytokines. Path analyses were adopted to further explore the associations between SDOH, comorbidities, and cytokines. Results: Among the 570 women, 45.79% had a diagnosis of BC. Over half (50.97%) had ER/PR+, HER2-, and 27.80% had triple negative BC. Results from Chi-square tests showed that a higher percentage of women with obesity (p=.001), HTN (p&amp;lt;.0001), and T2D (p=.024) had a BC diagnosis than those without the comorbidity. Women with obesity had significantly higher levels of Leptin, VEGFα, and MIP1b; women with HTN had significantly higher levels of VEGFα and MIP1b; and women with T2D had significantly higher levels of Leptin and TGFβ1/β2. Leptin was found significantly higher in ER/PR+ BC (p&amp;lt;.0001) and VEGFα was significantly higher in triple negative BC (p=.001). Increasing VEGFα and TGFβ1/β2 reduced BC disease-free survival significantly. The path model showed community poverty and education level did not affect TGFβ1/β2 directly but were indirectly associated with them through obesity and T2D status (p&amp;lt;.01). Community poverty level was indirectly associated with the level of MIP1b through HTN status (p&amp;lt;.01). Conclusions: To eliminate breast cancer disparities, effective interventions are needed that account for the social and community contexts in which women live and are treated. Interventions that target comorbidities of T2D, HTN, and obesity are important to reduce the disparities. Citation Format: Weizhou Tang, Yanyuan Wu, Jaydutt Vadgama. Social determinants of health and comorbidities increasing inflammation cytokines related to breast cancer in African American and Latinx women [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B150.

Yoyo Dieting, Post-Obesity Weight Loss, and Their Relationship with Gut Health.

Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed "yoyo dieting" and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.

Barriers to a Healthy Lifestyle Among Obese Patients Attending Primary Care Clinics in Al-Ahsa, Saudi Arabia.

Obesity is a significant public health issue in Saudi Arabia, contributing to high morbidity and mortality rates. This study aimed to identify the barriers preventing obese patients from adhering to healthy diets and regular exercise while following a health coach in primary healthcare centers in Al-Ahsa. A cross-sectional study of 283 obese adults revealed that major barriers included lack of energy, willpower, and time for exercise, as well as lack of willpower, social influence, and time for maintaining a healthy diet. These barriers were significantly associated with demographic factors such as obesity grade, comorbidities, and educational level. Addressing these barriers is essential for developing effective interventions to support lifestyle changes in obese patients.

Metabolically “extremely unhealthy” obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project

BackgroundThere is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia).MethodsWe analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1–2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese “extremely unhealthy”); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1–2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese “extremely unhealthy”). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke.Results2105 people with DM were included [median age 60 (IQR 45–70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06–13.47, respectively). On interaction analysis, in “extremely unhealthy” persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged < 65 years compared to older adults (Pint= 0.028).ConclusionBoth non-obese and obese people with DM and 3 associated CKM comorbidities represent an “extremely unhealthy” phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach.

Mediterranean diet and exercise are associated with better disease control in psoriatic arthritis.

Psoriatic arthritis (PsA) is associated with obesity and other related comorbidities, which impose an additional burden on disease activity and response to treatment. We investigated the impact of Mediterranean diet, and exercise on the presentation and severity of PsA. Three hundred fifty-five patients with PsA (n = 279) and psoriasis (PsO) (n = 76) were included in a cross-sectional study. Demographic and clinical characteristics and dietary and exercise patterns were recorded. Patients were grouped into (i) high, moderate, and low Mediterranean diet adherence and (ii) high, medium, and low activity level. Levels of diet and exercise were correlated with disease activity indices. PsA patients had more comorbidities than their PsO counterparts (42.7% vs. 26.3%, p = .038). The majority showed a low exercise pattern (total = 71.3%, PsA = 72.4%, PsO = 67.1%). Approximately half (total = 44.2%, PsA = 43.4%, PsO = 47.4%) did not follow a Mediterranean diet. Disease Activity in Psoriatic Arthritis Score (DAPSA) (p = .004), tender (p = .003) and swollen (p = .015) joint counts, erythrocyte sedimentation rate (ESR) (p = .001), and Psoriasis Area and Severity Index (PASI) (p = .015) had an inverse correlation with exercise. Higher Mediterranean diet adherence was associated with reduced ESR (p = .056), PASI (p = .011), and body surface area (BSA) (p = .009) indices. After adjusting for body mass index (BMI), exercise retained its positive correlation with PsA disease activity, but diet showed significant correlation only with enthesitis (p = 0.015). Uptake of a Mediterranean diet and exercise have positive effects on PsA activity, independently of BMI. These findings support lifestyle recommendations to supplement conventional treatment for improvement in disease outcomes. Key points • Diet and lifestyle are important influencers of health-related outcomes in PsA. • In this cross-sectional study of 355 patients with psoriatic disease, we found that Med Diet and exercise improve outcomes in PsA independently of weight loss. • Our results suggest that diet and lifestyle modifications should supplement conventional medical treatments.

Flavopiridol inhibits adipogenesis and improves metabolic homeostasis by ameliorating adipose tissue inflammation in a diet-induced obesity model

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA). The present study aimed to investigate the effect of flavopiridol on adipocyte differentiation and to determine the underlying mechanism. Flavopiridol inhibited adipocyte differentiation in different cell models like 3T3-L1, C3H10T1/2, and hMSCs at 150 nM. Flavopiridol was around 135 times more potent than its parent molecule rohitukine. The effect was mediated through down-regulation of key transcription factors of adipogenesis i.e. Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and their downstream targets, including adipocyte protein −2 (aP2) and fatty acid synthase (FAS). Further, results revealed that flavopiridol arrested the cell cycle in G1/S phase during mitotic clonal expansion by suppressing cell cycle regulatory proteins i.e. Cyclins and CDKs. Flavopiridol inhibited insulin-stimulated signalling in the early phase of adipocyte differentiation by downregulation of AKT/mTOR pathway. In addition, flavopiridol improved mitochondrial function in terms of increased oxygen consumption rate (OCR) in mature adipocytes. In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.

Impact of Diabetes Mellitus and Obesity Comorbidities on Survival Outcomes after Hepatocellular Carcinoma Resection: A Multicenter Retrospective Study

Introduction: This study aimed to evaluate the association of obesity and diabetes mellitus (DM) comorbidity with hepatocellular carcinoma (HCC) recurrence and survival. Methods: We investigated 1,644 patients who underwent hepatic resection for solitary HCC without vascular invasion using computed tomography. Patients were categorized into four groups according to the combination of obesity and DM comorbidities: OB (+) or (−) and DM (+) or (−). Postoperative cumulative recurrence rates within and beyond 2 years and beyond 5 years were assessed. Results: Multivariate Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (HRs) of reduced recurrence-free survival was 1.10 (95% confidence interval [CI]: 0.91–1.33; p = 0.31), 0.94 (95% CI: 0.78–1.12; p = 0.48), and 1.24 (95% CI: 1.01–1.54; p = 0.045) in the OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups compared with the OB(−)DM(−) group, respectively. Additionally, the corresponding adjusted HRs of reduced overall survival were 0.93 (p = 0.57), 0.97 (p = 0.76), and 1.38 (p = 0.013) for OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups, respectively. No significant difference in the early recurrence rate was determined among the four groups. The OB(+)DM(+) group demonstrated an increased risk for late recurrence beyond 2 years and 5 years postoperatively compared with the OB(−)DM(−) group (HR: 1.51; p = 0.024 and HR: 2.53; p = 0.046, respectively). The OB(+)DM(−) and OB(−)DM(+) groups demonstrated an increased risk for late recurrence beyond 5 years postoperatively (HR: 3.83; p < 0.001 and HR: 1.95; p = 0.037, respectively). Conclusions: Obesity and DM coexistence increased late recurrence and worsened prognosis in patients with HCC undergoing hepatic resection. The results help surgeons develop possible different surveillance protocol and need to focus on diabetes/obesity control during life-long surveillance for patients with HCC.

Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats

BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here.MethodsHealthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing.ResultsIncreased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (− 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray–Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats.ConclusionsIn the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.Graphical abstract

A Review on in-vivo and in-vitro Models of Obesity and Obesity-Associated Co-Morbidities.

Obesity is becoming a global pandemic with pandemic proportions. According to the WHO estimates, there were over 1.9 billion overweight individuals and over 650 million obese adults in the globe in 2016. In recent years, scientists have encountered difficulties in choosing acceptable animal models, leading to a multitude of contradicting aspects and incorrect outcomes. This review comprehensively evaluates different screening models of obesity and obesity-associated comorbidities to reveal the advantages and disadvantages/limitations of each model while also mentioning the time duration each model requires to induce obesity. For this review, the authors have gone through a vast number of article sources from different scientific databases, such as Google Scholar, Web of Science, Medline, and PubMed. In-vivo models used to represent a variety of obesity-inducing processes, such as diet-induced, drug-induced, surgical, chemical, stress-induced, and genetic models, are discussed. Animal cell models are examined with an emphasis on their use in understanding the molecular causes of obesity, for which we discussed in depth the important cell lines, including 3T3-L1, OP9, 3T3-F442A, and C3H10T1/2. Screening models of obesity-associated co-morbidities like diabetes, asthma, cardiovascular disorders, cancer, and polycystic ovarian syndrome (PCOS) were discussed, which provided light on the complex interactions between obesity and numerous health problems. Mimicking obesity in an animal model reflects multifactorial aspects is a matter of challenge. Future studies could address the ethical issues surrounding the use of animals in obesity research as well as investigate newly developed models, such as non-mammalian models. In conclusion, improving our knowledge and management of obesity and related health problems will require ongoing assessment and improvement of study models.

Randomized Controlled Trial Based US Commercial Payor Cost-Effectiveness Analysis of Endoscopic Sleeve Gastroplasty Versus Lifestyle Modification Alone for Adults With Class I/II Obesity.

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive day procedure that the MERIT randomized controlled trial (RCT) has demonstrated to be an effective and safe method of weight loss versus lifestyle modification alone. We sought to evaluate the cost-effectiveness of ESG from the perspective of a US commercial payer in a cohort of adults with class II and class I obesity with diabetes based on this RCT. We used a Markov modelling approach with BMI group health states and an absorbing death state. Baseline characteristics, utilities, BMI group transition probabilities, and adverse events (AEs) were informed by patient-level data from the MERIT RCT. Mortality was estimated by applying BMI-specific hazard ratios to US general population mortality rates. We used BMI-based health state utilities to reflect the impact of obesity comorbidities and applied disutilities due to ESG AEs. Costs included intervention costs, AE costs, and BMI-based annual direct healthcare costs to account for costs associated with obesity comorbidities. A willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was assumed. In our base-case analysis over a 5-year time horizon, ESG was cost-effective versus lifestyle modification alone with an incremental cost-effectiveness ratio of $23,432/QALY. ESG remained cost-effective in all sensitivity analyses we conducted and was dominant in analyses with longer time horizons. ESG is a cost-effective treatment option for people living with obesity and should be considered in commercial health plans as an additional treatment option for clinically eligible patients.