Role Of Obesity Research Articles

The role of obesity in mortality from digestive diseases in UK Biobank

Most current studies use body mass index (BMI) or waist circumference (WC) to define obesity, and BMI, which reflects subcutaneous fat independent of visceral fat, is the most commonly used indicator of obesity. WC reflects subcutaneous and visceral fat. This research aims to investigate the effect of obesity on mortality in people with digestive diseases. According to BMI and WC, we divided patients with obesity into the following four groups: general obesity, abdominal obesity, combined obesity, and non-obese. The effects of different obesity types on mortality in a population with digestive diseases were analysed via Cox regression and inverse probability-weighted Cox regression. Our research employed multivariate imputation via the chained equations method to interpolate missing values. A total of 254,445 participants, with a mean age of 57.8 ± 7.8 years, were included in the analysis. Of these participants, 227,111 (89.3%) participants were censored, and 27,334 (10.7%) participants died. Abdominal obesity and combined obesity were independent predictors of mortality in patients with digestive diseases. The combination of BMI and WC was valuable and significant for considering the type of obesity. In addition, our study revealed that sex, socioeconomic status, lifestyle habits, and physical activity were also associated with death in people with digestive disorders. Combined obesity, which is determined by both BMI and WC, is an important factor that influences mortality in a population with digestive diseases, and it plays a stronger role than abdominal obesity alone. These modifiable risk factors for mortality can provide guidance to populations with digestive diseases to avoid poor lifestyles and prolong survival time.

Is choline kinase alpha a drug target for obesity?

Choline kinase alpha (ChoKα) is a therapeutic target being developed for a variety of diseases, from cancer to rheumatoid arthritis and from parasites to bacterial infections. Nevertheless, the therapeutic potential of this drug target seems not exhausted and may end up as a possible solution for a larger variety of conditions. Here we present our working model for how ChoKα could play a role in obesity and for how drugs being developed as therapeutics for other diseases using ChoKα as a target, could be repurposed as prophylactic treatments for obesity. We also present preliminary observations in support of our model.

Genetic associations of metabolic factors and therapeutic drug targets with polycystic ovary syndrome

IntroductionPolycystic ovary syndrome (PCOS) is frequently accompanied with metabolic dysfunctions, yet the causal relationships between metabolic factors and PCOS remain to be conclusively established and etiology-based therapies are lacking. ObjectivesTo comprehensively identify the metabolic causal factors and potential drug targets for PCOS. MethodsThis genetic association study was conducted using bidirectional two-sample Mendelian Randomization (MR), multivariable MR (MVMR) and drug-target MR. Considering metabolic sexual dimorphism, female-specific genome-wide association studies (GWASs) for metabolic factors were obtained. To ensure the robustness of the findings, an additional independent PCOS GWAS dataset was utilized for replication. ResultsThe PCOS cohort included 10,074 PCOS cases (mean age 28 to 45 years) and 103,164 controls (mean age 27 to 60 years) of European ancestry. All participants were female. Employing two-sample MR analysis, we found that genetically proxied body mass index (BMI) (OR = 3.40 [95 % CI, 2.65–4.36]), triglyceride (TG) (OR = 1.54 [95 % CI, 1.17–2.04]), low-density lipoprotein cholesterol (LDL-c) (OR = 1.37 [95 % CI, 1.07–1.76]), and type 2 diabetes (T2D) (OR = 1.24 [95 % CI, 1.09–1.41]) were significantly associated with an increased risk of PCOS, whereas genetically predicted high-density lipoprotein cholesterol (HDL-c) (OR = 0.61 [95 % CI, 0.47–0.80]) decreased the odds of PCOS. Stepwise MVMR established a hierarchy of interactions among these metabolic factors, identifying BMI and HDL-c as the most prominent causal factors. Notably, drug-target MR analysis identified incretin-based therapeutics, PCSK9 inhibitors, LPL gene therapy, sulfonylureas, and thiazolidinediones as potential therapeutics for PCOS. All these findings were validated in an independent dataset. ConclusionThis study offered insights into the roles of obesity, diabetes, and dyslipidemia in PCOS etiology and therapeutics, underscoring the necessity for managing metabolic health in women and paving the way for tailored therapeutic strategies for PCOS based on its metabolic underpinnings.

European Association for the Study of Obesity (EASO) Position Statement on Medical Nutrition Therapy for the Management of Individuals with Overweight or Obesity and Cancer.

Obesity, a prevalent and multifactorial disease, is linked to a range of metabolic abnormalities, including insulin resistance, dyslipidemia, and chronic inflammation. These imbalances not only contribute to cardiometabolic diseases but also play a significant role in cancer pathogenesis. The rising prevalence of obesity underscores the need to investigate dietary strategies for effective weight management for individuals with overweight or obesity and cancer. This European Society for the Study of Obesity (EASO) position statement aimed to summarize current evidence on the role of obesity in cancer and to provide insights on the major nutritional interventions, including the Mediterranean diet (MedDiet), the ketogenic diet (KD), and the intermittent fasting (IF), that should be adopted to manage individuals with overweight or obesity and cancer. The MedDiet, characterized by high consumption of plant-based foods and moderate intake of olive oil, fish, and nuts, has been associated with a reduced cancer risk. The KD and the IF are emerging dietary interventions with potential benefits for weight loss and metabolic health. KD, by inducing ketosis, and IF, through periodic fasting cycles, may offer anticancer effects by modifying tumor metabolism and improving insulin sensitivity. Despite the promising results, current evidence on these dietary approaches in cancer management in individuals with overweight or obesity is limited and inconsistent, with challenges including variability in adherence and the need for personalized dietary plans.

Trends in risk factor prevalence in young adults experiencing acute coronary syndrome

Abstract Introduction While for many decades the prevalence of coronary artery disease (CAD) and acute coronary syndrome (ACS) has been declining, it seems as this trend has reached a plateau, mostly in developing countries, but also in developed countries due to reasons such as immigration and unhealthy lifestyle concomitant to the pandemic of obesity and metabolic syndrome. Still, CAD remains the leading cause of death globally. Preventive cardiology guidelines addressed adequate control of traditional risk factors in order to reduce CAD burden, mortality and morbidity but to lesser extent fewer resources were invested for the younger population in their third or fourth decade for implementing this practical guideline. As global obesity pandemic emerged over the past decades, it emphasizes the need to re-evaluating risk factors, particularly the role of obesity and metabolic syndrome, in contributing to the rising incidence of ACS among the younger population. Purpose The study aims to analyze trends in risk factors among young adult which presented with ACS from 2005 to 2022. Results may inform targeted interventions and deepen understanding of ACS pathophysiology and severity. Methods The study encompassed 712 patients hospitalized between 2005 and 2022. Comparable groups were analyzed, including temporal changes, ST-elevation myocardial infarction (STEMI) vs. non-ST-elevation myocardial infarction (NSTEMI), different age groups, and various ethnicities. Categorical values were thoroughly examined, yielding insightful results. Results Temporal changes revealed that patients presenting with ACS before 2014 exhibited a higher incidence of Dyslipidemia and familial history (p=0.002 and p=0.005). Conversely, in the latter period, overweight and diabetes were more significant (p<0.001 and p=0.0176). In the STEMI vs. NSTEMI group, smoking was more prevalent in the STEMI group (p=0.0449), while diabetes, Dyslipidemia, and hypertension were more significant for the NSTEMI group (p=0.022, p=0.009, p<0.001). For the age group, the only observed difference was in hypertension for the 40-45 and 45-50 age group (p=0.0463). In the ethnicity group, individuals of Arab origin exhibited higher rates of smoking and familial cardiac background (p<0.001 and p=0.03), while in the non-Arab group, obesity was more significant (p<0.001). Conclusion The observed changes in the distribution of risk factors among patients with CAD align with global trends, indicating an increase in obesity. Belonging to the overweight population, prior to obesity, pose a prominent risk factor for ACS. Smoking remains a significant factor, with higher rates in patients presenting with STEMI, aligning previous research and re-emphasize the importance of prevention. Different demographic groups may exhibit distinct risk factors contributing to the common endpoint of CAD. Tailored intervention strategies considering diverse risk profiles are essential for effective coronary disease prevention.

DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort.

Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

GR113808, a serotonin receptor 4 antagonist, prevents high-fat-diet-induced obesity, fatty liver formation, and insulin resistance in C57BL/6J mice

BackgroundThe burden of nonalcoholic fatty liver disease is increasing, and limited therapeutic drugs are available for its treatment. Serotonin binds to approximately 14 serotonin receptors (HTR) and plays diverse roles in obesity and metabolic complications. In this study, we focused on the function of HTR4 on nonalcoholic fatty liver disease using GR113808, a selective HTR4 antagonist.MethodsMale C57BL/6J mice were fed high-fat diet for 12 weeks with intraperitoneal GR113808 injection, and HTR expression, weight changes, glucose and lipid metabolism, hepatic fat accumulation, changes in adipose tissue, the changes in transcriptional factors of signaling pathways, and inflammations were assessed. Hep3B cells and 3T3-L1 cells were treated with siRNA targeting HTR4 to downregulate its expression and then cultured with palmitate to mimic a high-fat diet. The changes in transcriptional factors of signaling pathways, and inflammations were assessed in those cells.ResultsAfter feeding a high-fat diet to male C57BL/6J mice, HTR4 expression in the liver and adipose tissues decreased. GR113808 suppressed body weight gain and improved glucose intolerance. Furthermore, GR113808 not only decreased fatty liver formation but also reduced adipose tissue size. Additionally, GR113808 reduced inflammatory cytokine serum levels and inflammasome complex formation in both tissues. Palmitate treatment in HTR4-downregulated Hep3B cells, also reduced peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein-1 pathway induction as well as inflammasome complex formation, thus decreasing inflammatory cytokine levels. HTR4 downregulation in 3T3-L1 cells also reduced palmitate-induced inflammasome complex formation and inflammatory cytokine production. Palmitate-induced insulin resistance in Hep3B cells, but not in 3T3-L1 cells, was improved by HTR4 downregulation.ConclusionsIn summary, GR113808 protected against fatty liver formation and improved inflammation in the liver and adipose tissue. Downregulation of HTR4 ameliorated insulin resistance in the liver. These results suggest that HTR4 could serve as a promising therapeutic target for metabolic diseases.

Low-intensity pulsed ultrasound improves metabolic dysregulation in obese mice by suppressing inflammation and extracellular matrix remodeling

Chronic inflammation in white adipose tissue is crucial in obesity and related metabolic disorders. Low-intensity pulsed ultrasound (LIPUS) is renowned for its anti-inflammatory effects as a non-invasive treatment, yet its precise role in obesity has been uncertain. Our study investigates the therapeutic effect of LIPUS and its underlying mechanism on obesity in mice, thereby offering a novel approach for non-invasive treatment of obesity and associated metabolic disorders for human. Male C57BL/6J mice aged 10 weeks were fed a high-fat diet (HFD) for 8 weeks to establish obesity model, then underwent 8 weeks of LIPUS (frequency: 1.0 MHz, duty cycle: 20 %, Isata: 58–61 mW/cm2, 20 min per day) stimulation of the epididymal white adipose tissue. Fat and lean mass were measured using nuclear magnetic resonance (NMR), while energy homeostasis was evaluated using metabolic cages. Insulin resistance was assessed using glucose tolerance tests (GTT) and insulin tolerance tests (ITT). Regulatory mechanisms were explored using RNA sequencing. Results showed that LIPUS significantly reduced obesity markers in obese mice, including body and adipose tissue weight, and improved insulin resistance, without affecting food intake. RNA sequencing showed 250 up-regulated and 351 down-regulated genes between HFD-LIPUS group and HFD-Sham group, suggesting anti-inflammatory action. Quantitative PCR confirmed reduced pro-inflammatory gene expression and macrophage infiltration in eWAT. Gene set enrichment analysis showed decreased NF-κB signaling and extracellular matrix-receptor interactions in LIPUS-treated mice. Thus, LIPUS effectively mitigates metabolic dysregulation in HFD-induced obesity through inflammation suppression and extracellular matrix remodeling, which provides a potential physical therapy for metabolic syndrome in clinic.

Assessment of salivary and serum leptin in tobacco smokers and oral squamous cell carcinoma-A case-control study

ObjectivesOral squamous cell carcinoma (OSCC) is the most common head and neck malignancy and tobacco-related cancers account for a significant portion of all oral cancers. Cancer patients often suffer from cachexia, which contributes significantly to mortality. Leptin is a protein released by adipocytes identified to play an important role in obesity and inflammation. The present study aimed to quantify and compare salivary and serum leptin in tobacco smokers and OSCC. Materials and MethodsThe present prospective case-control study enrolled 42 subjects divided equally among OSCC and tobacco smokers without oral lesions (TS). Both saliva and blood were collected from each subject and leptin levels were determined using enzyme-linked immunosorbent assay. The data obtained were analysed using Mann Whitney U, Kruskal Wallis, Friedman, and Spearman correlation tests (p < 0.05). ResultsA significant reduction in both salivary and serum leptin levels in OSCC was observed (p < 0.001, 0.002 respectively). In addition, significant reductions in weight and body mass index were also observed during follow-ups at 3, 6, and 9 months (p < 0.001 for both). ConclusionsReduced salivary and serum leptin levels in OSCC proved that it is an important diagnostic marker, with non-invasive saliva measurement being more patient-friendly. Future multicentric studies with higher samples in OSCC subgroups are warranted. Clinical RelevanceLeptin reduction in oral squamous cell carcinoma proved to be an important diagnostic marker. Non-invasive salivary techniques could be employed in mass screening programmes. The significant correlation between leptin and BMI also shed insight into the overall well-being of the patient.

Regulating role of Pleurotus ostreatus insoluble dietary fiber in high fat diet induced obesity in rats based on proteomics and metabolomics analyses

This study aims to reveal the effects of Pleurotus ostreatus insoluble dietary fiber (POIDF) on liver protein and cecal metabolites in obese rats and its potential mechanism by intestinal microbes. It was found that POIDF contained the structural characteristics of cellulose and hemicellulose, as well as amorphous diffraction peaks. POIDF could reduce the body weight and organ index of obese rats, regulate dyslipidemia, and improve the pathological changes of liver and epididymis fat. Further experimental results showed that POIDF could regulate the abundance of bacteria related to lipid metabolism, and maintain intestinal homeostasis. The metabolomics results showed that the fatty acyls pathway in the cecum contents was the pathway with the highest concentration of small molecule metabolites. POIDF supplementation regulated the expression of liver key proteins, as well as biosynthesis of amino acids, steroid biosynthesis, arachidonic acid metabolism and PPAR signaling pathway. Omics association analysis found that POIDF could further regulate liver proteins and their signaling pathways, regulate the levels of fatty acyls and amino acid metabolites in the gut and the enrichment of related pathways, and play a therapeutic or preventive role in obesity after degradation by intestinal microbiota.

Growth hormone attenuates obesity and reshapes gut microbiota in high-fat diet-fed mice

Growth hormone (GH) and gut microbiota are key regulators of metabolism and have been linked to the development and treatment of obesity. Although variations in GH levels are associated with changes in gut microbiota composition, the specific effects of GH on gut microbiota and its role in obesity remain unclear. This study explored the effects of various GH doses (0.25, 0.75 and 1.5 IU/kg) on adipose tissue mass and gut microbiota in high-fat diet-induced obese mice. Notably, high-dose GH (1.5 IU/kg) significantly reduced the adipose tissue mass. This dose also reversed high-fat diet-induced gut microbiota dysbiosis, restoring microbial diversity and increasing the abundance of beneficial genera such as Ruminococcaceae and Muribaculaceae. Additionally, high-dose GH normalized several obesity-related gut microbiota pathways, including starch and sucrose metabolism, galactose metabolism, and secondary bile acid biosynthesis. GH therapy also improved intestinal barrier function, a key determinant of gut microbial homeostasis. These findings underscore the therapeutic potential of GH in obesity management through its effects on gut microbiota, providing new avenues for obesity interventions.

Пухлина Бреннера у жінок репродуктивного віку з ожирінням: клініко-морфологічний аналіз випадків із практики

Background. Brenner tumors are rare epithelial ovarian tumors, the incidence of which among all ovarian tumors ranges from 0.6 to 2%. Considering the rarity of the pathology and absence of specific clinical symptoms, the authors present an analysis of own cases from the practice of Brenner tumor. Purpose – familiarization of the medical community with the clinical and morphological features of Brenner tumor in obese women of reproductive age based on an analysis of own practice cases. Materials and Methods. A clinical and morphological analysis of cases from practice of Brenner tumor of different histological variants in obese women of reproductive age is provided. Results. In the first case, in patient V., 42 years old, with obesity, a morphological study of the surgical material was diagnosed a benign variant of the Brenner tumor in the left ovary, which clinically manifested by pain and was not diagnosed by ultrasound. In the second case, in patient G., 36 years old, with obesity, it was morphologically diagnosed a benign variant of Brenner tumor in the right ovary, and borderline variant of Brenner tumor in the left ovary against the background of a benign variant. Brenner tumor in patient G. manifested by pain, infertility in anamnesis, and the presence of cysts on ultrasound examination. The menstrual cycle disorders in women in both cases may be caused by the presence of leiomyomas in the uterus or Brenner tumors or a combination of these tumor pathology. Conclusions. Brenner tumors are rare epithelial ovarian tumors, the only diagnostic method for which is a morphological examination of surgical material. Literature data about the role of obesity in the genesis of the development of these epithelial ovarian tumors, the presence in the described cases from practice of an increased body mass index in women with benign and borderline variants of Brenner tumors actualize the conduct of complex morphological studies in order to search, firstly, the etiopathogenetic features of the development of these ovarian tumors in obese women, and secondly, the morphological differential diagnostic criteria for these epithelial ovarian tumors in women with and without obesity.

The Impact of Gastrointestinal Hormones on Human Adipose Tissue Function

Background: Obesity is a global issue, the development of which depends on many interacting factors. Among these, hormones secreted in the gastrointestinal tract play an important role. The aim of this review was to assess the impact of these hormones on the functions of adipose tissue. Methods: The analysis was based on the latest research concerning both adipose tissue and gastrointestinal hormones. Results: It was found that these hormones can significantly affect adipose tissue, both directly and indirectly. Some hormones, when secreted in excess, can stimulate adipose tissue formation processes, while others can inhibit them. The impact of hormones depends on the location and type of adipose tissue as well as the physiological state of the body. It should also be noted that no hormone acts in isolation but in close cooperation with other factors. Conclusions: The relationship between gastrointestinal hormones and adipose tissue, and their role in obesity, is a complex and evolving field of study. Further research is necessary, particularly into the interactions between hormones and other factors, as well as their mutual interactions.

The phenotype of the pediatric patient with Cushing syndrome but without obesity.

Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings. Cohort study. We analyzed 273 patients with young onset of CS at ≤18 years old and who were classified as patients with or without obesity based on their BMI z scores. Patients without obesity (n = 84, 31%) were more frequently females with an older age of onset compared with patients with obesity (n = 189, 69%). Consistent with their older age, patients without obesity were also more likely to have advanced Tanner stages. Patients with and without obesity had a similar duration of disease, but patients with obesity showed higher markers of hypercortisolemia (urinary free cortisol, UFC). A higher prevalence of hypertension and insulin resistance was seen in patients with obesity than those without obesity, adjusting for UFC (P < .05 for all comparisons). While fatty liver disease was not statistically different among the entire cohort, elevated alanine transaminase and metabolic dysfunction-associated steatotic liver disease scores were more common in ACTH-dependent CS patients with obesity (P < .05). Weight gain appears to mediate some but not all the cortisol-associated complications in pediatric CS. Therefore, obesity may be a modifiable risk factor among these patients.

Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice.

Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.

Interleukin-27 signaling resists obesity by promoting the accumulation of Treg cells in visceral adipose tissue

The prevalence of obesity and its associated metabolic disorders has emerged as one of the most significant health threats worldwide. The visceral adipose tissue regulatory T cells (VAT Treg) play an essential role in maintaining homeostasis and preventing obesity mainly by secreting Interleikin-10 (IL-10) and Transforming Growth Factor β (TGF-β). However, the mechanism that regulates VAT Treg quantity and function remains unclear. Here we elucidate the pivotal role of IL-27 signaling in sustaining the accumulation of VAT Treg cells, thereby conferring protection against obesity. We found that mice with the deficiency of IL-27 receptor Wsx1 gained more body weight and VAT weight than their wild-type littermates when fed both a normal-fat diet (NFD) and a high-fat diet (HFD). Notably, the population of VAT Treg cells was reduced in Wsx1 knockout (KO) mice, regardless of whether they were fed a normal-fat diet (NFD) or a high-fat diet (HFD). Correspondingly, the expression levels of the transcription factors FOXP3 and PPAR-γ, essential for VAT Treg function, were also diminished in Wsx1 KO mice. Taken together, our findings indicate that IL-27 signaling plays a protective role in obesity by supporting the maintenance and accumulation of VAT Treg cells.

Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review.

Depression affects several aspects of life, including socioeconomic status, relationships, behavior, emotions, and overall health. The etiology of depression is complex and influenced by various factors, with obesity emerging as a significant contributor. This narrative review aims to investigate the factors associated with the development of depression, with a particular focus on the role of obesity. The literature search was conducted on PubMed, Embase, and PsycINFO from May to July 2024. The review highlights the impact of environmental and socioeconomic conditions; lifestyle choices, including physical activity and dietary habits; stress; traumatic experiences; neurotransmitter imbalances; medical and psychological conditions; hormone fluctuations; and epigenetic factors on depression. A key emphasis is placed on the inflammatory processes linked to obesity, which may drive the bidirectional relationship between obesity and depression. The findings suggest that obesity is associated with an increased risk of depression, potentially due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management. Understanding these interconnected factors is important for developing targeted interventions to address both obesity and depression, leading to improved quality of life for those affected.

262 - The role of obesity and continuous glucose monitoring metrics for predicting adverse perinatal outcomes in individuals with type 1 diabetes

262 - The role of obesity and continuous glucose monitoring metrics for predicting adverse perinatal outcomes in individuals with type 1 diabetes

The role of receptor activity-modifying proteins in obesity and diabetes mellitus.

Receptor activity-modifying proteins (RAMPs) modulate the expression and activity of numerous G protein-coupled receptors, primarily those within class B1. These receptors have important physiological roles, including in the regulation of food intake, energy metabolism, and glucose homeostasis. Dysregulation of these pathways can lead to obesity and diabetes mellitus, which present an ever-expanding global challenge. Whilst the roles of class B1 receptors and their peptide agonists in obesity and diabetes have been investigated, the contribution of RAMPs is less well understood. This review summarises the results of RAMP knockout studies, highlighting the involvement of these proteins in the incidence of disease. It then moves to discuss how receptor, RAMP, and agonist expression changes in disease states, and the benefits (or detriments) of these agonists to the pathways implicated in disease pathophysiology. Whilst much of the data centres around the calcitonin family of receptors, as their interactions with RAMPs are well established, this review then discusses receptors whose role in obesity and diabetes is well founded, but the significance of whose interactions with RAMPs is more recently emerging. The conclusion of this study of the literature is, however, that the information surrounding RAMPs is conflicting and multifaceted, and more research is required to fully understand their contribution to obesity and diabetes.

Z-Spectral MRI Quantifies the Mass and Metabolic Activity of Adipose Tissues With Fat-Water-Fraction and Amide-Proton-Transfer Contrasts.

Brown adipose tissue (BAT) is metabolically activatable and plays an important role in obesity and metabolic diseases. With reduced fat-water-fraction (FWF) compared with white adipose tissue (WAT), BAT mass and its functional activation may be quantified with Z-spectra MRI, with built-in FWF and the metabolic amide proton transfer (APT) contrasts. To investigate if Z-spectral MRI can quantify the mass and metabolic activity of adipose tissues. Prospective. Seven groups of 8-week-old male rats, including two groups (n = 7 per group) for in vivo MRI study and five groups (n = 5 per group) for ex vivo validation; 12 young and healthy volunteers with 6 male and 6 female. The 7 T small animal and 3 T clinical systems, T2-weighted imaging, Rapid Acquisition with Relaxation Enhancement (RARE) readout based chemical exchange saturation transfer (CEST) Z-spectral MRI sequence. Quantified FWF and APT from Z-spectra in rats before and after norepinephrine (NE) stimulation and in healthy human subjects; ex vivo measurements of total proteins in BAT from rats. Two-tailed unpaired Student's t-tests and repeated measures ANOVA. P-value <0.05 was considered significant. Decreased FWF (from 39.6% ± 7.2% before NE injection to 16.4% ± 7.2% 120 minutes after NE injection, P < 0.0001) and elevated APT (from 1.1% ± 0.5% before NE injection to 2.9% ± 0.5% 120 minutes after NE injection, P < 0.0001) signals in BAT were observed with in vivo Z-spectral MRI in rats injected with NE at 7 T MRI. At clinical 3 T, Z-spectral MRI was used to quantify the FWF (58.5% ± 7.2% in BAT and 73.7% ± 6.5% in WAT with P < 0.0001) and APT (2.6% ± 0.8% in BAT and 0.9% ± 0.3% in WAT with P < 0.0001) signals in healthy volunteers. APT signals of BAT were negatively correlated with the BMI in humans (r = 0.71). Endogenous Z-spectral MRI was demonstrated to simultaneously quantify BAT mass and function based on its FWF and APT contrasts. 1.