Obese Research Articles

Genetic variants of LEAP2 are associated with anthropometric traits and circulating insulin-like growth factor-1 concentration: A UK Biobank study.

To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity. Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted. Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes. These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.

Dietary patterns interfere with gut microbiota to combat obesity.

Obesity and obesity-related metabolic disorders are global epidemics that occur when there is chronic energy intake exceeding energy expenditure. Growing evidence suggests that healthy dietary patterns not only decrease the risk of obesity but also influence the composition and function of the gut microbiota. Numerous studies manifest that the development of obesity is associated with gut microbiota. One promising supplementation strategy is modulating gut microbiota composition by dietary patterns to combat obesity. In this review, we discuss the changes of gut microbiota in obesity and obesity-related metabolic disorders, with a particular emphasis on the impact of dietary components on gut microbiota and how common food patterns can intervene in gut microbiota to prevent obesity. While there is promise in intervening with the gut microbiota to combat obesity through the regulation of dietary patterns, numerous key questions remain unanswered. In this review, we critically review the associations between dietary patterns, gut microbes, and obesity, aiming to contribute to the further development and application of dietary patterns against obesity in humans.

Protein-coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex-dependently in rats.

Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2nd transmembrane (TM) helix of Adcy3 in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior. We used CRISPR-SpCas9 to mutate the TM domain of Adcy3 in WKY rats (Adcy3mut/mut). We also created a heterozygous knockout rat in the same strain (Adcy3+/-). Wild-type (WT), Adcy3+/-, and Adcy3mut/mut rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion-like behaviors, and memory. Adcy3+/- and Adcy3mut/mut rats weighed more than WT rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3mut/mut males displayed increased passive coping and decreased memory while Adcy3mut/mut females displayed increased anxiety-like behavior. These studies show that the ADCY3 TM domain plays a role in protein function, that Adcy3 may contribute to the relationship between obesity and MDD, and that sex influences the relationships between Adcy3, metabolism, and behavior.

739-P: Efficacy and Safety of Tirzepatide in Overweight (OW) and Obese (OB) Patients with Type 1 Diabetes (T1D)

739-P: Efficacy and Safety of Tirzepatide in Overweight (OW) and Obese (OB) Patients with Type 1 Diabetes (T1D)

2075-LB: Identification and Characterization of Two Novel Data-Driven Subtypes of Human Obesity

2075-LB: Identification and Characterization of Two Novel Data-Driven Subtypes of Human Obesity

Modulation of gut microbiota by crude gac aril polysaccharides ameliorates diet-induced obesity and metabolic disorders

Obesity is a global health challenge that causes metabolic dysregulation and increases the risk of various chronic diseases. The gut microbiome is crucial in modulating host energy metabolism, immunity, and inflammation and is influenced by dietary factors. Gac fruit (Momordica cochinchinensis), widely consumed in Southeast Asia, has been proven to have various biological activities. However, the composition and effect of crude gac aril polysaccharides (GAP) on obesity and gut microbiota disturbed by high-fat diet (HFD) remain to be elucidated. Compositional analysis showed that GAP contains high oligosaccharides, with an average of 7–8 saccharide units. To mimic clinical obesity, mice were first made obese by feeding HFD for eight weeks. GAP intervention was performed from week 9 to week 20 in HFD-fed mice. Our results showed that GAP inhibited body weight gain, eWAT adipocyte hypertrophy, adipokine derangement, and hyperlipidemia in HFD-induced obese mice. GAP improved insulin sensitivity, impaired glucose tolerance, and hepatic steatosis. GAP modulated the gut microbiota composition and reversed the HFD-induced dysbiosis of at least 20 genera. Taken together, GAP improves metabolic health and modulates the gut microbiome to relieve obesity risk factors, demonstrating the potential of dietary GAP for treating obesity-associated disorders.

Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity.

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2Mb in size (B6.TH-Chr1-16.2Mb). Both male and female B6.TH-Chr1-16.2Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.

Pet microbiota and its relationship with obesity

The incidence of obesity in pets appears to be increasing in line with the increasing incidence of obesity in humans, and leads to decreased life expectancy. Obesity, which is considered a multifactorial disease caused by excessive adiposity, leads to a decrease in quality of life and serious health problems. It is known that there is an increase in the incidence of respiratory disorders, cardiological disorders, metabolic and endocrine problems, orthopedic diseases and some types of cancer in obese cats and dogs. There are many factors in the formation of obesity. One of these factors is the balance of the microbiota in gut. Many studies have shown that the microbiota affects critical steps in the formation of obesity and there are strong relationships between dietary content, microbiota, and obesity. In particular, high-fat diets are known to increase microbiome composition in terms of gram-negative bacterial strains and trigger dysbiosis. Again, in cases where dysbiosis occurs, the levels of volatile fatty acids also vary and lead to undesirable results through hormonal mechanisms. This condition, which causes hyperphagia, hypertriglyceridemia and insulin resistance, increases the incidence of obesity and diabetes mellitus. The ratio of Firmicutes and Bacteroidetes, which are among the largest phylae of the microbiota, shows serious differences when compared in underweight and obese animals. In this article, these relationships between microbiota and obesity are reviewed.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. Six trials comprising 3928 patients and 12048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Harnessing the melanocortin system in the control of food intake and glucose homeostasis

The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.

Impact of body mass index and karyotype on clinical outcomes in adolescents and young adults (AYA) with acute myeloid leukemia.

6551 Background: Acute myelogenous leukemia (AML) represents 15%–20% of leukemias in children and approximately 33% in adolescents and young adults (AYA) (1). Obesity has been associated with worse outcome in acute lymphoblastic leukemia in AYA patients (pts). To date, however, the relationship between weight and clinical outcomes in AYA pts diagnosed with AML has not been established. We investigated the impact of body mass index (BMI) along with other prognostic factors on outcomes of AYA AML pts receiving intensive chemotherapy and/or allogeneic stem cell transplant (SCT). Methods: This retrospective chart review included pts 18-39 yrs newly diagnosed with AML between 01/2006-12/2023. All pts received intensive chemotherapy with cytarabine- and anthracycline-based induction followed by consolidation chemotherapy +/- SCT. BMI was calculated using height and weight at AML diagnosis. Pts were classified by BMI into under, normal, overweight, or obese categories. AML risk classification (ELN 2022) and HCT co-morbidity index (HCT-CI) were performed. Outcomes included complete response (CR), CR with incomplete counts (CRi), overall response rates (CR+CRi), event free survival (EFS), and overall survival (OS). Results: Eighty-seven pts (median age 25 yrs, range 18-38) were identified. 44 (51%) were male; 85% were Caucasian. Per ELN 2022, 27 (31%) had favorable, 40 (46%) intermediate, and 20 (23%) adverse risk. Overall response rate to chemotherapy was 92% (CR 80%, CRi 12%). CR rate by ELN was 96%, 72% and 58%, respectively. Median OS for all pts was 788 days and per ELN risk was 1379, 569, and 595 days, respectively. Co-morbidity indices (HCT-CI) ranged from 0-5. Sixty-two percent underwent SCT. 29% relapsed. The percentage of pts alive at 2 and 5 years was 54% and 29%. Pts were categorized by BMI: underweight (BMI < 18.5, 6%), normal weight (NW) (BMI 18.5-24.9) (37%), overweight (OW)(BMI 25-29, 26%), and obese (OB) (BMI > 30, 31%) pts. Overall, there was a trend to improved outcomes in NW vs OW and OB pts. Median OS was 1006 (NW) vs 748 (OW) vs 678 (OB) days (p=0.0036 for NW vs OW/OB). Two-year OS was 63%, 52%, and 48%; 5-year OS was 38%, 26%, and 19%. The impact of BMI was dependent on AML karyotype. In favorable risk AML AYA pts, the relapse rate was 4%, 4% and 12%. Median OS was 1982 (NW), 1169 (OW), and 1256 (OB) days (p=0.0525 NW vs OW/OB). Five-year OS was 50%, 25% and 18%. The most common causes of death were GVHD-induced multi-organ failure and respiratory failure which did not correlate with HCT-CI. In intermediate and adverse risk AML, there was no difference in outcomes by BMI. Conclusions: Outcomes of favorable risk AYA AML pts following intensive chemotherapy +/- SCT was influenced by BMI with increased mortality and shorter OS in pts with high BMI (overweight and obese) as compared to normal BMI. Additional studies to confirm this finding and elucidate the underlying reasons are warranted.

Association between metabolically healthy obesity and risk of dementia: A systematic review and meta‐analysis

AbstractBackgroundSome studies suggest that the metabolic alterations linked to obesity in humans may increase the likelihood of developing dementia. However, there are currently no existing meta‐analyses exploring the possible occurrence of dementia in patients with metabolically healthy obesity (MHO). In the present study, we aimed to investigate a potential correlation between individuals with MHO and the likelihood of developing dementia.MethodOur research focused on searching three databases to locate pertinent studies starting from January 10, 2023. We used sensitivity analysis, the Egger's test, and a visual funnel plot to separately assess the reliability of the research results and publication bias. We conducted this study according to a pre‐established protocol in the PROSPERO registry (CRD42023449459).ResultsWe incorporated three potential cohort investigations. Individuals with good metabolic health and obesity showed a decreased likelihood of developing dementia compared with those who were metabolically healthy but not obese (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.68–0.92). In contrast, individuals who were metabolically unhealthy and nonobese had an increased likelihood of developing dementia (HR = 1.33; 95% CI 1.25–1.42), whereas the population with metabolically unhealthy obesity did not exhibit a notable association with dementia onset (HR = 1.06; 95% CI 0.83–1.37).ConclusionAccording to our meta‐analysis, patients with MHO had a reduced likelihood of developing general dementia and Alzheimer disease. Maintaining a well‐functioning metabolism can provide advantages in reducing the occurrence of dementia.

How does bariatric surgery remodel adipose tissue?

This lecture delves into the pivotal role of adipose tissue in obesity and its response to weight loss, particularly via bariatric surgery. Adipose tissue, responsible for storing excess energy, undergoes significant changes during obesity, marked by inflammation and fibrosis. Bariatric surgery, serving as a model, allow the exploration of adipose tissue remodeling post-weight loss, inducing metabolic and fibro-inflammatory shifts. Despite successful weight loss, inflammation and fibrosis persist, as evidenced by changes in immune cells, altered cytokine profiles and the accumulation of extracellular matrix (ECM). Unfortunately, these lingering effects impair the normal adipose tissue function. In this context, adipose progenitors, an heterogenous resident population of mesenchymal stromal cells, display functions important to fibrosis development, capable of differentiating into myofibroblasts and contributing to ECM deposition. Particularly, a distinct subpopulation of adipose progenitors with high CD9 expression (CD9high) is associated with fibrosis and insulin resistance in human obesity. The persistence of fibrosis post-weight loss poses challenges, correlating with metabolic dysfunction despite improved glucose tolerance. A comprehensive understanding of the mechanisms driving adipose tissue remodeling and fibrosis post-weight loss is imperative for the development of effective treatments for obesity. The intricate interplay between adipose tissue, inflammation, and fibrosis underscores the necessity for further in-depth research to elucidate these mechanisms and formulate targeted therapies for obesity-related complications.

#Headlesspreggos: challenging visual imaginaries of pregnancy and reproduction

Amid new abortion restrictions in the USA, scientific advances in genetic technologies and investigations of COVID-19 vaccinations in pregnancy, news stories about reproduction abound, often accompanied by images of what...

Visual perception of group fatness as a precursor to social identity threat and safety

ABSTRACT Across two studies (N = 190), we evaluate how fat people perceive groups of bodies and how this visual processing predicts social identity threat and safety. We examined how fat people ensemble code – rapidly and simultaneously extract visual information from a group – body size from groups of bodies. Stimuli included sets of 3-d modeled bodies varying in body mass index (BMI; Study 1) and real photographs of groups of people with known BMI (Study 2). As hypothesized, we found that fat people were generally accurate at ensemble coding the average body size of arrays after 500 ms exposure, and that, particularly among fat people with medium and high stigma consciousness, arrays of increasing average BMI were associated with heightened feelings of identity safety. Our work suggests that the representation of fatness in one’s environment may be an important precursor to social identity threat and safety processes.

#670 Clinical characteristics of sarcopenic obesity in hemodialysis patients

Abstract Background and Aims Sarcopenia is associated with all-cause mortality in older dialysis patients. Although obesity is a risk factor for a variety of diseases in the general population, obese hemodialysis patients have a survival advantage over lean patients. Some hemodialysis patients are obese but have reduced muscle mass, a condition known as sarcopenic obesity. The characteristics and diagnostic criteria for sarcopenic obesity in dialysis patients remain unclear. This study aims to determine the prevalence and clinical characteristics of patients at risk for sarcopenia or sarcopenic obesity. Method The dialysis centers involved in this study were four dialysis centers belonging to Seiei-kai Medical Corporation. Hemodialysis patients attending these facilities were included. Obesity was defined as a BMI of 25 kg/m2 or higher, and sarcopenia risk was described as a SARC-F questionnaire score of 4 or higher and a sit-to-stand test (SS-5) of 12 seconds or longer. Patients were classified as sarcopenic obese if they met both criteria. Patients classified as obese (OB) or sarcopenic obesity (SO) were compared for the following factors: age, history of dialysis, sex ratio, presence of diabetes, blood biochemical tests, Kt/V, nPCR, %CGR, number of falls in the past year, and symptoms using the Patients Reported Outcomes Measure (PROM). Results We analyzed the cross-sectional data of 622 patients attending our four dialysis centers. The prevalence of SO among all patients was 6% (34 patients), and OB was 26% (164 patients); Hb (10.9 ± 1.5 vs. 11.4 ± 1.2 g/dl; p=0.03), albumin (3.40 ± 0.3 vs. 3.63 ± 0.3 mg/dl; p<0.01) and nPCR (0.82 ± 0.16 vs. 0.91 ± 0.13 g/kg/day; p=0.01) were significantly lower in the SO group than in the OB group. Age (72.4 ± 9.2 vs. 32.9 ± 12.7 years; p<0.01) was higher in the SO group, and patients with a history of falls were significantly more likely to be in the SO group (59% vs. 29%; p<0.01). Symptom severity as measured by the PROM was also higher in the SO group. Conclusion This study showed that patients in the SO group were more likely to fall and had inadequate protein intake. In addition, patients in the SO group are older and have more severe PROM symptoms. Interventions to increase muscle strength and improve physical function should be considered for patients with SO. Nutritional support, treatment of individual symptoms, and exercise therapy will be necessary, and these interventions may be complex and challenging. We will design an observational study on the prognostic impact of sarcopenic obesity. A limitation of this study is that we used the SARC-F questionnaire and SS-5 rather than the AWGS criteria to assess sarcopenia, which may not have captured true sarcopenia.

An Interdisciplinary Collaboration to Reduce Weight Stigma Among Exercise Professionals

Weight stigma is the negative social judgment of people based on their weight. Despite the negative consequences of weight stigma, its prevalence is well-documented including within the physical activity (PA) landscape. Research shows that a wide range of PA-related professionals hold negative attitudes toward fat people, including physical education teachers, kinesiology students, and fitness trainers. This article describes a collaboration across disciplines and fields to develop a weight stigma reduction intervention for exercise professionals. Weight Inclusive Thinking for Fitness Spaces (WIT FITS) is a two-hour, self-paced, interactive online course grounded in the Health at Every Size® paradigm and research-informed strategies for improving exercise professionals’ attitudes toward fatness and fostering weight inclusivity in fitness settings. WIT FITS was the result of a three-year interdisciplinary collaboration with scholars from pedagogy, public health, sport and exercise psychology, and nutrition. Community partners involved in the development, implementation, and evaluation of WIT FITS included body liberation activists, web and instructional designers, and campus recreation leaders.

Obesity Alters POMC and Kisspeptin Neuron Cross Talk Leading to Reduced Luteinizing Hormone in Male Mice.

Obesity is associated with hypogonadism in males, characterized by low testosterone and sperm number. Previous studies determined that these stem from dysregulation of hypothalamic circuitry that regulates reproduction, by unknown mechanisms. Herein, we used mice fed chronic high-fat diet, which mimics human obesity, to determine mechanisms of impairment at the level of the hypothalamus, in particular gonadotropin-releasing hormone (GnRH) neurons that regulate luteinizing hormone (LH), which then regulates testosterone. Consistent with obese humans, we demonstrated lower LH, and lower pulse frequency of LH secretion, but unchanged pituitary responsiveness to GnRH. LH pulse frequency is regulated by pulsatile GnRH secretion, which is controlled by kisspeptin. Peripheral and central kisspeptin injections, and DREADD-mediated activation of kisspeptin neurons, demonstrated that kisspeptin neurons were suppressed in obese mice. Thus, we investigated regulators of kisspeptin secretion. We determined that the LH response to NMDA was lower in obese mice, corresponding to fewer glutamate receptors in kisspeptin neurons, which may be critical for kisspeptin synchronization. Given that kisspeptin neurons also interact with anorexigenic POMC neurons, which are affected by obesity, we examined their cross talk, and determined that the LH response to either DREADD-mediated activation of POMC neurons or central injection of αMSH, a product of POMC, is abolished in obese mice. This was accompanied by diminished levels of αMSH receptor, MC4R, in kisspeptin neurons. Together, our studies determined that obesity leads to the downregulation of receptors that regulate kisspeptin neurons, which is associated with lower LH pulse frequency, leading to lower LH and hypogonadism.

Improving dietary patterns in obese mice: Effects on body weight, adiposity, anhedonia-like behavior, pro-BDNF expression and 5-HT system

IntroductionThe excessive fat accumulation in obesity, resulting from an unbalanced diet, can lead to metabolic and neurological disorders and increase the risk of developing anxiety and depression. AimAssess the impact of dietary intervention (DI) on the serotonergic system, brain-derived neurotrophic factor (BDNF) expression and behaviors of obese mice. MethodsMale C57BL/6 mice, 5 weeks old, received a high-fat diet (HFD) for 10 weeks for the induction of obesity. After this period, for 8 weeks, half of these animals received a control diet (CD), group obese (OB) + control diet (OB + CD, n = 10), and another half continued being fed HFD, group obese + HFD (OB + HFD, n = 10). At the end of the eighth week of intervention, behavioral tests were performed (sucrose preference test, open field, novel object recognition, elevated plus maze and tail suspension). Body weight and food intake were assessed weekly. Visceral adiposity, the hippocampal and hypothalamic protein expression of BDNF, 5-HT1A (5-HT1A serotonin receptor) and TPH2 (key enzyme in serotonin synthesis), were evaluated after euthanasia. ResultsThe dietary intervention involved changing from a HFD to a CD over an 8-week period, effectively reduced body weight gain, adiposity, and anhedonia-like behavior. In the OB + HFD group, we saw a lower sucrose preference and shorter traveled distance in the open field, along with increased pro-BDNF expression in the hypothalamus compared to the OB + CD mice. However, the levels of TPH2 and 5-HT1A remained unchanged. ConclusionThe HFD model induced both obesity and anhedonia, but the dietary intervention successfully improved these conditions.

Study of Thyroid Function Tests in Patients with Metabolic Syndrome

Study of Thyroid Function Tests in Patients with Metabolic Syndrome