Development Of Cardiometabolic Diseases Research Articles

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Funding Acknowledgements None. Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and major adverse cardiovascular events in patients with established CVD. The value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease. The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components (prediabetes, low HDL-C levels, high triglyceride levels, increased waist circumference and high-risk for MASLD) after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels and increased triglyceride levels after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio (OR:1.017, 95% CI: 1.006-1.028, P=0.003) and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Production of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism

Alterations in gut microbiota composition are suggested to contribute to cardiometabolic diseases, in part by producing bioactive molecules. Some of the metabolites are produced by very low abundant bacterial taxa, which largely have been neglected due to limits of detection. However, the concentration of microbially produced metabolites from these taxa can still reach high levels and have substantial impact on host physiology. To explore this concept, we focused on the generation of secondary bile acids by 7α-dehydroxylating bacteria and demonstrated that addition of a very low abundant bacteria to a community can change the metabolic output dramatically. We show that Clostridium scindens converts cholic acid into the secondary bile acid deoxycholic acid (DCA) very efficiently even though the abundance of C. scindens is low, but still detectable by digital droplet PCR. We also show that colonization of germ-free female mice with a community containing C. scindens induces DCA production and affects host metabolism. Finally, we show that DCA correlates with impaired glucose metabolism and a worsened lipid profile in individuals with type 2 diabetes, which implies that this metabolic pathway may contribute to the development of cardiometabolic disease.

Cardiovascular health and cancer risk associated with plant based diets: An umbrella review.

Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide. This umbrella review aims at assessing the impact of animal-free and animal-products-free diets (A/APFDs) on the risk factors associated with the development of cardiometabolic diseases, cancer and their related mortalities. PubMed and Scopus were searched for reviews, systematic reviews, and meta-analyses published from 1st January 2000 to 31st June 2023, written in English and involving human subjects of all ages. Primary studies and reviews/meta-analyses based on interventional trials which used A/APFDs as a therapy for people with metabolic diseases were excluded. The umbrella review approach was applied for data extraction and analysis. The revised AMSTAR-R 11-item tool was applied to assess the quality of reviews/meta-analyses. Overall, vegetarian and vegan diets are significantly associated with better lipid profile, glycemic control, body weight/BMI, inflammation, and lower risk of ischemic heart disease and cancer. Vegetarian diet is also associated with lower mortality from CVDs. On the other hand, no difference in the risk of developing gestational diabetes and hypertension were reported in pregnant women following vegetarian diets. Study quality was average. A key limitation is represented by the high heterogeneity of the study population in terms of sample size, demography, geographical origin, dietary patterns, and other lifestyle confounders. Plant-based diets appear beneficial in reducing cardiometabolic risk factors, as well as CVDs, cancer risk and mortality. However, caution should be paid before broadly suggesting the adoption of A/AFPDs since the strength-of-evidence of study results is significantly limited by the large study heterogeneity alongside the potential risks associated with potentially restrictive regimens.

Fat-associated lymphoid clusters: Supporting visceral adipose tissue B cell function in immunity and metabolism.

It is now widely understood that visceral adipose tissue (VAT) is a highly active and dynamic organ, with many functions beyond lipid accumulation and storage. In this review, we discuss the immunological role of this tissue, underpinned by the presence of fat-associated lymphoid clusters (FALCs). FALC's distinctive structure and stromal cell composition support a very different immune cell mix to that found in classical secondary lymphoid organs, which underlies their unique functions of filtration, surveillance, innate-like immune responses, and adaptive immunity within the serous cavities. FALCs are important B cell hubs providing B1 cell-mediated frontline protection against infection and supporting B2 cell-adaptative immune responses. Beyond these beneficial immune responses orchestrated by FALCs, immune cells within VAT play important homeostatic role. Dysregulation of immune cells during obesity and aging leads to chronic pathological "metabolic inflammation", which contributes to the development of cardiometabolic diseases. Here, we examine the emerging and complex functions of B cells in VAT homeostasis and the metabolic complications of obesity, highlighting the potential role that FALCs play and emphasize the areas where further research is needed.

Inflammatory Bowel Disease exercise and diet (IBDeat) habits study: exploring lifestyle habits and cardiometabolic disease risk factors

Patients with inflammatory bowel disease (IBD) have higher risk of developing cardiometabolic diseases due to chronic gut and systemic inflammation which promotes atherogenesis. Adopting healthy lifestyle habits can prevent development of cardiometabolic diseases, but can be challenging for people with IBD. The IBD exercise and diet (IBDeat) habits study describes the lifestyle habits and cardiometabolic disease risk factors of adults with IBD in Aotearoa, New Zealand (NZ).This is a cross-sectional study including adult NZ IBD patients recruited online via Crohn’s and Colitis NZ and Dunedin hospital from 2021 to 2022. An online questionnaire collected demographics, smoking status, comorbidities, medications, disease severity scores, quality of life, physical activity, and dietary intake. The Dunedin cohort had physical measurements taken including anthropometrics, handgrip strength, blood pressure, body composition (bioelectrical impedance), blood nutritional markers, and faecal calprotectin. Data were compared to established reference values and linear regression analysis investigated associations between lifestyle habits and cardiometabolic risk factors. The study received University of Otago ethical approval (reference: H21/135). A total of 213 adults with IBD (54% Crohn’s disease; 46% ulcerative colitis) completed the online questionnaire and a subset of 102 from Dunedin provided physical measurements. Participants characteristics were: median age 37 (IQR 25, 51) years, 71% female, 82% NZ European, 4% smokers, and 1.4% had active IBD. Thirty-five percent of participants had at least one comorbidity and 34% of participants had poor quality of life. Known dietary risk factors associated with cardiometabolic diseases were common: low intakes of vegetables (77%), fruit (51%), fibre (35%) and high intakes of total fat (84%) and saturated fat (98%). Physical activity recommendations were met by 61% of participants and 63% reported barriers to being more active from fatigue (63%) and joint pain (54%). Other cardiometabolic risk factors were common in the Dunedin cohort: high LDL (79%) and total cholesterol (76%), central adiposity (64%), high body fat percentage (44%), high blood pressure (26%), and low handgrip strength (25%). Regression analysis showed that vegetable (per serve) and carbohydrate (per 5% of total daily energy intake (TE)) were associated with 0.22 mmol/L (95%CI 0.43, 0.013) and 0.20 mmol/L (95%CI 0.34, 0.057) lower LDL cholesterol. Discretionary food items were associated with higher LDL cholesterol, 0.11 mmol/L per daily serve (95%CI 0.028, 0.19). A 5% difference in TE intake from carbohydrate was associated with 1.11% (95%CI 2.22%, 0.0038%) lower body fat percentage while protein was associated with 3.1% (95%CI 0.81%, 5.39%) higher body fat percentage. Physical activity had weak associations with cardiometabolic disease risk factors. Adults with IBD have multiple modifiable risk factors for cardiometabolic diseases. Vegetable and carbohydrate intake were associated with lower LDL cholesterol concentration while discretionary food items showed otherwise. Protein intake was associated with higher body fat percentage.

Association of adiposity indicators with cardiometabolic multimorbidity risk in hypertensive patients: a large cross-sectional study.

Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.

Weight Gain in Midlife Women.

To summarize the evidence and clinical implications of weight and body composition changes during midlife in women and provide an overview of weight gain prevention and management in this population. Aging-related changes such as decreased energy expenditure and physical activity are important culprits for weight gain in midlife women. The hormonal changes of menopause also influence body adiposity distribution and increase central adiposity. These body changes can have health consequences including the development of cardiometabolic diseases, osteoarthritis, cancer, worsening in cognition, mental health, and menopause symptoms. Midlife women experience changes related to aging, menopause, and lifestyle which favor weight gain. Clinical practice should focus on early counseling and anticipatory guidance on the importance of dietary changes and physical activity to attenuate this phenomenon. Future research should focus on the longitudinal relationship between weight trends in midlife and health consequences and mortality.

Lifestyle Factors and Cardiovascular Health: The Gut-Heart Axis

An emerging direction of research focuses on the gut microbiome as a complex, metabolically active system whose metabolites can impact the development of cardiometabolic diseases by directly influencing the phenotype of the host.

Vitamin D levels and lipid profile in children and adolescents: a tight correlation.

Vitamin D is an essential hormone for humans, playing an important role in musculoskeletal and calcium homeostasis. Its deficiency/insufficiency seems to contribute to the development of cardiometabolic diseases in adults: this correlation appears less clear for children and adolescents. The aim of this paper was to review literature data on the relationship between vitamin D and lipid profile alterations in pediatric population. We carried out a comprehensive research in electronic databases, including MEDLINE and PubMed up to December 2022, for cross-sectional or prospective studies that investigated the correlation between serum vitamin D levels and lipid profile in children and adolescents. At the end of the process, 37 articles were included in this review. According to our findings, vitamin D deficiency/insufficiency is strongly associated with lower high-density lipoprotein (HDL) cholesterol levels and higher levels of triglycerides and total cholesterol. Data about low-density lipoproteins (LDL) cholesterol are inconsistent. The potential role of vitamin D supplements for the prevention of cardiometabolic disease currently remains a speculation. An increasing number of studies shows how hypovitaminosis D in the pediatric age may play a role in the pathogenesis of metabolic disorders and lipid profile alterations. Data regarding the potential role of vitamin D supplements for the prevention of cardiometabolic disease are currently controversial. Further studies are needed to evaluate the causality of this association and to assess the underlying pathogenetic mechanisms.

New prospects for the interdisciplinary use of metformin in clinical practice: its role in the treatment of non-alcoholic fatty liver disease

Today, despite the introduction of primary and secondary prevention methods, chronic non-communicable diseases remain the main cause of high morbidity and mortality throughout the world. According to some studies, hepatic component metabolic syndrome and one of the main factors contributing to the development of cardiometabolic diseases is non-alcoholic severe liver disease. According to the results of studies, NAFLD is currently the leading cause of chronic liver diseases worldwide and is closely associated with the development of cardiometabolic pathology, in particular type 2 diabetes and CVD. This review is devoted to the epidemiology, pathophysiology of the close relationship between NAFLD and type 2 diabetes, as well as therapy affecting insulin resistance, a key link connecting these two nosologies.

Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults.

The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases. Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors. The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured. Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ -0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight-obese participants than in metabolically healthy overweight-obese participants. Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.

Probiotic and Muscadine Grape Extract Interventions Shift the Gut Microbiome and Improve Metabolic Parameters in Female C57BL/6 Mice.

Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake.

Childhood BMI trajectories predict cardiometabolic risk and stress at age 13 years. The STARS cohort

Abstract Background Research on BMI trajectory focuses mainly on childhood and adolescence, missing birth and infancy, which are also relevant in the development of cardiometabolic disease. We aimed to identify trajectories of BMI from birth throughout childhood, and to examine whether BMI trajectories predict health at age13 years; and, if so, whether differences exist among trajectories regarding timeframes during which early life BMI influences health. Methods Participants from Western Sweden (n = 1902, 44% males, 13.5±0.4 years) completed questionnaires assessing perceived stress and psychosomatic symptoms and examined for waist circumference (WC), systolic blood pressure (SBP), pulse wave velocity, and white blood cell counts (WBC). They had at least 5 retrospective measures of weight and height covering birth, infancy, childhood to early adolescence. We used group-based trajectory modeling to identify BMI trajectories and linear regression to assess associations, which are presented as estimated mean differences with 95% CI between trajectories. Results We identified three BMI trajectories: normal, moderate, and excessive gain. Differences distinguishing these trajectories were established before 2 years of age. After adjusting for sex, age, migrant background, and parental income, adolescents with excessive gain had higher WC (19.2 [18.4-20.0} cm), SBP (3.6 [2.4-4.4] mmHg), WBC (0.7 [0.4-0.9] x109/L) and stress (1.1 [0.2-1.9]) than adolescents with normal gain. Increased levels of WC (6.4 [5.8-6.9] cm), SBP (1.8 [1.0-2.5] mmHg) and stress (0.7 [0.1-1.2]) were found in adolescents with moderate gain. The observed significant positive correlation of early life BMI with SBP started approximately at age 6 years for participants with excessive gain, much earlier than for participants with normal and moderate gain, for which it started at age 12 years. Conclusions Excessive gain BMI trajectory from birth predicts cardiometabolic risk and stress in adolescents before age 13 years. Key messages • Differences distinguishing childhood BMI trajectories were established before age 2 years. • In excessive gain group, influence of early life BMI on SBP started already around age 6 years.

Per- and polyfluoroalkyl substances and cardiometabolic diseases: A review.

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi-omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

Exploring targeted preventive health check interventions – a realist synthesis

BackgroundPreventive health checks are assumed to reduce the risk of the development of cardio-metabolic disease in the long term. Although no solid evidence of effect is shown on health checks targeting the general population, studies suggest positive effects if health checks target people or groups identified at risk of disease. The aim of this study is to explore why and how targeted preventive health checks work, for whom they work, and under which circumstances they can be expected to work.MethodsThe study is designed as a realist synthesis that consists of four phases, each including collection and analysis of empirical data: 1) Literature search of systematic reviews and meta-analysis, 2) Interviews with key-stakeholders, 3) Literature search of qualitative studies and grey literature, and 4) Workshops with key stakeholders and end-users. Through the iterative analysis we identified the interrelationship between contexts, mechanisms, and outcomes to develop a program theory encompassing hypotheses about targeted preventive health checks.ResultsBased on an iterative analysis of the data material, we developed a final program theory consisting of seven themes; Target group; Recruitment and participation; The encounter between professional and participants; Follow-up activities; Implementation and operation;Shared understanding of the intervention; and Unintended side effects. Overall, the data material showed that targeted preventive health checks need to be accessible, recognizable, and relevant for the participants’ everyday lives as well as meaningful to the professionals involved.The results showed that identifying a target group, that both benefit from attending and have the resources to participate pose a challenge for targeted preventive health check interventions. This challenge illustrates the importance of designing the recruitment and intervention activities according to the target groups particular life situation.ConclusionThe results indicate that a one-size-fits-all model of targeted preventive health checks should be abandoned, and that intervention activities and implementation depend on for whom and under which circumstances the intervention is initiated. Based on the results we suggest that future initiatives conduct thorough needs assessment as the basis for decisions about where and how the preventive health checks are implemented.

OR15-03 Lower Hepatic Mitochondrial Respiration Relates To Dysmetabolism In Adolescents With Severe Obesity

Abstract Disclosure: E. Finn: None. K.N. Fuller: None. L.A. Knaub: None. Y. Garcia Reyes: None. S.C. Derderian: None. J. Schoen: None. T. Inge: None. J.E. Reusch: Advisory Board Member; Self; Medtronic Diabetes. K. Nadeau: None. M. Cree: None. Introduction: The severity of metabolic disease in youth with obesity is varied and determinants of disease progression are not known. Non-alcoholic fatty liver disease appears to be central to the development of cardiometabolic disease in youth with severe obesity. We tested the hypothesis that hepatic mitochondrial respiratory capacity would correlate with cardiometabolic measures in youth with severe obesity and a range of glycemia. Methods: Adolescents with severe obesity and a range of dysglycemia undergoing bariatric surgery were enrolled. Participants underwent anthropomorphic assessments, fasting labs, and a 4-hour mixed meal tolerance test (MMTT, 45 g carbs, 14 g protein, and 14 g fat) over 30 minutes followed by serial measures of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and free fatty acids. Liver biopsies obtained at time of vertical sleeve gastrectomy surgery were analyzed for mitochondrial respiration. Permeabilized liver tissue was assessed for mitochondrial oxygen consumption by respirometry (Oxygraph-2k, OROBOROS) under both pyruvate (carbohydrate) and palmitoyl-carnitine (lipids) substrate conditions. Results: Fifteen youth with severe obesity (female=60%, mean age 16.9 ± 1.5 years, mean BMI 47.4 ± 7.2 kg/m2) were enrolled. Lower hepatic carbohydrate-supported respiration relates to higher serum glucose concentrations throughout the 4-hr MMTT (P=&amp;lt; 0.001 to 0.05) as well as higher fasting serum triglycerides (p =&amp;lt;0.001-0.05). Lower liver lipid-supported respiration is associated with higher C-peptide levels (p =0.001-0.01) throughout MMTT, increased Matsuda Index (p =0.001-0.05), and higher fasting hepatic transaminases, alanine aminotransferase (p =0.006-0.04), aspartame aminotransferase (p =0.007-0.02), and gamma-glutamyl transferase (p =0.01-0.03). Insulin, GLP-1, and free fatty acids are not correlated with mitochondrial respiration. Conclusion: Consistent with findings in adults and animals, youth with severe obesity have lower hepatic mitochondrial respiration which correlates with markers of poorer cardiometabolic health including higher triglycerides, higher glucose concentraions, lower insulin sensitivity, higher insulin secretion (C-peptide), and higher liver transaminases. Based on these findings, dysregulated hepatic mitochondrial respiration should be further explored as a possible contributor to the development of early liver disease and glucose dysregulation. Presentation: Friday, June 16, 2023

Macrophage-associated markers of metaflammation are linked to metabolic dysfunction in pediatric obesity

BackgpoundMetabolically driven chronic low-grade adipose tissue inflammation, so-called metaflammation, is a central feature in obesity. This inflammatory tone is largely driven by adipose tissue macrophages (ATM), which express pro- and anti-inflammatory markers and cytokines such as, e.g., IL-1 receptor antagonist (IL-1RA), CD163 and osteopontin (OPN). Metaflammation ultimately leads to the development of cardiometabolic diseases. This study aimed to evaluate the association between selected adipose tissue macrophage-associated markers and metabolic comorbidities in pediatric obesity. MethodsFrom a pediatric cohort with obesity (n = 108), clinically thoroughly characterized including diverse routine blood parameters, oral glucose tolerance test and liver MRI, plasma IL-1RA, soluble (s)CD163 and OPN were measured by ELISA. ResultsWe observed significantly higher IL-1RA, sCD163, and OPN levels in the plasma of children with metabolic-dysfunction associated fatty liver disease (MAFLD) and metabolic syndrome. Moreover, IL-1RA and sCD163 correlated with hepatic disease and apoptosis markers alanine aminotransferase and CK-18. IL-1RA concentrations additionally correlated with insulin resistance, while children with disturbed glucose metabolism had significantly higher levels of sCD163. ConclusionMAFLD and other metabolic disorders in pediatric patients with obesity are associated with an elevation of adipose tissue macrophage-related inflammation markers.

Effects of aircraft noise cessation on blood pressure, cardio- and cerebrovascular endothelial function, oxidative stress, and inflammation in an experimental animal model

Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects of noise may persist in response to a noise-off period. We investigated the effects of acute aircraft noise exposure (mean sound level of 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction and increased blood pressure in male C57BL/6 J mice. 1, 2 or 4d of noise cessation after a 4d continuous noise exposure period completely normalized noise-induced endothelial dysfunction of the aorta (measured by acetylcholine-dependent relaxation) already after a 1d noise pause. Vascular oxidative stress and the increased blood pressure were partially corrected, while markers of inflammation (VCAM-1, IL-6 and leukocyte oxidative burst) showed a normalization within 4d of noise cessation. In contrast, endothelial dysfunction, oxidative stress, and inflammation of the cerebral microvessels of noise-exposed mice did not improve at all. These data demonstrate that the recovery from noise-induced damage is more complex than expected demonstrating a complete restoration of large conductance vessel function but persistent endothelial dysfunction of the microcirculation. These findings also imply that longer noise pauses are required to completely reverse noise-induced vascular dysfunction including the resistance vessels.

Sexual Dimorphism in Cardiometabolic Diseases: The Role of AMPK.

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability among both males and females. The risk of cardiovascular diseases is heightened by the presence of a risk factor cluster of metabolic syndrome, covering obesity and obesity-related cardiometabolic risk factors such as hypertension, glucose, and lipid metabolism dysregulation primarily. Sex hormones contribute to metabolic regulation and make women and men susceptible to obesity development in a different manner, which necessitates sex-specific management. Identifying crucial factors that protect the cardiovascular system is essential to enhance primary and secondary prevention of cardiovascular diseases and should be explicitly studied from the perspective of sex differences. It seems that AMP-dependent protein kinase (AMPK) may be such a factor since it has the protective role of AMPK in the cardiovascular system, has anti-diabetic properties, and is regulated by sex hormones. Those findings highlight the potential cardiometabolic benefits of AMPK, making it an essential factor to consider. Here, we review information about the cross-talk between AMPK and sex hormones as a critical point in cardiometabolic disease development and progression and a target for therapeutic intervention in human disease.

Dietary Sugars during Critical Phases of Development and Long-Term Risk of Non-Communicable Diseases

Obesity and the intake of high-sugar diets have dramatically increased in recent decades. However, it is still uncertain how sugar intake during the critical development phase affects the long-term health of children. In this context, the Developmental Origins of Health and Disease (DOHaD) concept established a correlation between early life environment and the development of cardiometabolic diseases in adulthood. This review summarizes the current knowledge about the consequences of sugar intake during the critical development phase for the onset of non-communicable diseases (NCDs). We found evidence that increased sugar intake during pregnancy contributes to maternal obesity and many cardiometabolic dysfunctions in the offspring. Furthermore, dietary sugar during the suckling period provokes the obese phenotype in adulthood. Finally, high-sugar diet intake during childhood induces metabolic syndrome and depressive-like behavior.