Obesity-driven mitochondrial dysfunction in human adipose tissue-derived mesenchymal stem/stromal cells involves epigenetic changes.

Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.

Tomato genotype but not crop water deficit matters for tomato health benefits in diet-induced obesity of C57BL/6JRj male mice.

Several studies have linked the intake of lycopene and/or tomato products with improved metabolic health under obesogenic regime. The aim was to evaluate the differential impact of supplementations with several tomato genotypes differing in carotenoid content and subjected to different irrigation levels on obesity-associated disorders in mice. In this study, 80 male C57BL/6JRj mice were assigned into 8 groups to receive: control diet, high fat diet, high fat diet supplemented at 5 % w/w with 4 tomato powders originating from different tomato genotypes cultivated under control irrigation: H1311, M82, IL6-2, IL12-4. Among the 4 genotypes, 2 were also cultivated under deficit irrigation, reducing the irrigation water supply by 50 % from anthesis to fruit harvest. In controlled irrigation treatment, all genotypes significantly improved fasting glycemia and three of them significantly lowered liver lipids content after 12 weeks of supplementation. In addition, IL6-2 genotype, rich in ß-carotene, significantly limited animal adiposity, body weight gain and improved glucose homeostasis as highlighted in glucose and insulin tolerance tests. No consistent beneficial or detrimental impact of deficit irrigation to tomato promoting health benefits was found. These findings imply that the choice of tomato genotype can significantly alter the composition of fruit carotenoids and phytochemicals, thereby influencing the anti-obesogenic effects of the fruit. In contrast, deficit irrigation appears to have an overall insignificant impact on enhancing the health benefits of tomato powder in this context, particularly when compared to the genotype-related variations in carotenoid content.

Combined impact of sleep and obesity on female infertility in the NHANES 2017-2020.

BACKGROUND: Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. METHODS: The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. RESULTS: This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49-3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03-2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28-3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17-3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24-4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01-3.49) were associated with increased odds of infertility, respectively. CONCLUSION: There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting.

Sarcopenic obesity (SO) is defined as the combination of excess fat mass (obesity) and low skeletal muscle mass and function (sarcopenia). The identification and classification of factors related to SO would favor better prevention and diagnosis. The present article aimed to (i) define a list of factors related with SO based on literature analysis, (ii) identify clinical conditions linked with SO development from literature search and (iii) evaluate their relevance and the potential research gaps by consulting an expert panel. From 4746 articles screened, 240 articles were selected for extraction of the factors associated with SO. Factors were classified according to their frequency in the literature. Clinical conditions were also recorded. Then, they were evaluated by a panel of expert for evaluation of their relevance in SO development. Experts also suggested additional factors. Thirty-nine unique factors were extracted from the papers and additional eleven factors suggested by a panel of experts in the SO field. The frequency in the literature showed insulin resistance, dyslipidemia, lack of exercise training, inflammation and hypertension as the most frequent factors associated with SO whereas experts ranked low spontaneous physical activity, protein and energy intakes, low exercise training and aging as the most important. Although literature and expert panel presented some differences, this first list of associated factors could help to identify patients at risk of SO. Further work is needed to confirm the contribution of factors associated with SO among the population overtime or in randomized controlled trials to demonstrate causality.

S-Methyl Cysteine Sulfoxide Does Not Ameliorate Weight Gain or Hyperlipidemia in Mice Fed a High-Fat Diet.

SCOPE: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed. METHODS AND RESULTS: Fifty C57BL/6 male mice are randomly assigned to standard-chow, high-fat, or high-fat supplemented with low-SMCSO (43 mg kg-1 body weight [BW] day-1), medium-SMCSO (153 mg kg-1 BW day-1), or high-SMCSO (256 mg kg-1 BW day-1) for 12-weeks. High-fat with SMCSO did not prevent diet-induced obesity, glucose intolerance, or hypercholesterolemia. Mice fed high-fat with SMCSO has higher hepatic lipids than mice fed standard-chow or high-fat alone. Urinary SMCSO increases at 6- and 12-weeks in the low-SMCSO group, before reducing 46% and 28% in the medium- and high-SMCSO groups, respectively, at 12-weeks, suggesting possible tissue saturation. Interestingly, two SMCSO-fed groups consume significantly more feed, without significant weight gain. Due to limitations in measuring consumed feed, caution should be taken interpreting these results. CONCLUSION: SMCSO (43-256 mg kg-1 BW day-1) does not ameliorate metabolic syndrome features in high-fat fed mice. Substantial knowledge gaps remain. Further studies should administer SMCSO separately (i.e., gavage), with metabolic studies exploring tissue levels to better understand its physiological action.

1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets.

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.

Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.

Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.

Neural correlates of obesity across the lifespan.

Associations between brain and obesity are bidirectional: changes in brain structure and function underpin over-eating, while chronic adiposity leads to brain atrophy. Investigating brain-obesity interactions across the lifespan can help better understand these relationships. This study explores the interaction between obesity and cortical morphometry in children, young adults, adults, and older adults. We also investigate the genetic, neurochemical, and cognitive correlates of the brain-obesity associations. Our findings reveal a pattern of lower cortical thickness in fronto-temporal brain regions associated with obesity across all age cohorts and varying age-dependent patterns in the remaining brain regions. In adults and older adults, obesity correlates with neurochemical changes and expression of inflammatory and mitochondrial genes. In children and older adults, adiposity is associated with modifications in brain regions involved in emotional and attentional processes. Thus, obesity might originate from cognitive changes during early adolescence, leading to neurodegeneration in later life through mitochondrial and inflammatory mechanisms.

HuR promotes triglyceride synthesis and intestinal fat absorption.

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

CVD incidence and mortality among people with diabetes and/or hypertension: Results from the English longitudinal study of ageing.

BACKGROUND AND AIMS: Diabetes and/or hypertension are the most common conditions in older people, and also related to higher cardiovascular disease (CVD) incidence and mortality. This study aims to explore the risk of CVD incidence and mortality among older people with diabetes and/or hypertension over a 16 years follow-up period and investigates the role of depression and obesity in these relationships. METHODS: 6,855 participants aged 50+ from the English Longitudinal Study of Ageing (ELSA). The main exposure is having diabetes and/or hypertension at baseline (2002/2003) compared to not having, but excluded those with coronary heart disease (CHD) and/or stroke (CVD). Survival models are used for CVD incidence and mortality up to 2018, adjusted for socio-demographic, health, health behaviours, cognitive function, and physical function characteristics. RESULTS: 39.3% of people at baseline had diabetes and/or hypertension. The risk of CVD incidence was 1.7 (95%CI: 1.5; 1.9) higher among people with diabetes and/or hypertension compared to those without and was independent of covariates adjustment. People with diabetes and/or hypertension were also 1.3 (95%CI: 1.1; 1.8) times more likely to die from CVD than those without. We did not find evidence for an elevated risk of CVD incidence and mortality among people with obesity nor among those with depression. CONCLUSIONS: In order to effectively reduce the risk of CVD incidence and mortality among older people, treatment as well as management of hypertension and diabetes should be routinely considered for older people with diabetes and/or hypertension.

Application of a transparent artificial intelligence algorithm for US adults in the obese category of weight.

OBJECTIVE AND AIMS: Identification of associations between the obese category of weight in the general US population will continue to advance our understanding of the condition and allow clinicians, providers, communities, families, and individuals make more informed decisions. This study aims to improve the prediction of the obese category of weight and investigate its relationships with factors, ultimately contributing to healthier lifestyle choices and timely management of obesity. METHODS: Questionnaires that included demographic, dietary, exercise and health information from the US National Health and Nutrition Examination Survey (NHANES 2017-2020) were utilized with BMI 30 or higher defined as obesity. A machine learning model, XGBoost predicted the obese category of weight and Shapely Additive Explanations (SHAP) visualized the various covariates and their feature importance. Model statistics including Area under the receiver operator curve (AUROC), sensitivity, specificity, positive predictive value, negative predictive value and feature properties such as gain, cover, and frequency were measured. SHAP explanations were created for transparent and interpretable analysis. RESULTS: There were 6,146 adults (age > 18) that were included in the study with average age 58.39 (SD = 12.94) and 3122 (51%) females. The machine learning model had an Area under the receiver operator curve of 0.8295. The top four covariates include waist circumference (gain = 0.185), GGT (gain = 0.101), platelet count (gain = 0.059), AST (gain = 0.057), weight (gain = 0.049), HDL cholesterol (gain = 0.032), and ferritin (gain = 0.034). CONCLUSION: In conclusion, the utilization of machine learning models proves to be highly effective in accurately predicting the obese category of weight. By considering various factors such as demographic information, laboratory results, physical examination findings, and lifestyle factors, these models successfully identify crucial risk factors associated with the obese category of weight.

Association between body mass index and prevalence of bacterial vaginosis: Results from the NHANES 2001-2004 study.

BACKGROUND: The impact of bacterial vaginosis on women's health is an increasing concern; however, the effect of the obesity index on bacterial vaginosis is controversial. We investigated the association between body mass index and bacterial vaginosis in women in the United States. METHODS: This was a cross-sectional study which obtained the data from the National Health and Nutrition Examination Survey from 2001 to 2004, in which weighted multivariate regression and logistic regression analyses were performed to explore the independent relationship between body mass index and bacterial vaginosis. Subgroup analyses and smoothed curve fitting were also performed. RESULTS: A total of 5,428 participants were enrolled, and the findings show that the participants with higher body mass index tended to have a higher incidence of bacterial vaginosis. In the fully adjusted model, a positive association between bacterial vaginosis and body mass index was observed (Odd's ratio = 1.03, 95% Confidence interval, 1.01-1.04). The subgroup analysis showed that this positive association was significant in non-Hispanic White individuals (Odd's ratio = 1.0327, 95% Confidence interval, 1.0163, 1.0493). CONCLUSION: Increased bacterial vaginosis positivity may be associated with an increased body mass index.

Association of body mass index and waist circumference with long-term mortality risk in 10,370 coronary patients and potential modification by lifestyle and health determinants.

BACKGROUND AND AIMS: Body adiposity is known to affect mortality risk in patients with coronary artery disease (CAD). We examined associations of body mass index (BMI) and waist circumference (WC) with long term mortality in Dutch CAD patients, and potential and effect modification of these associations by lifestyle and health determinants. METHODS: 10,370 CAD patients (mean age ∼65 y; 20% female; >80% on cardiovascular drugs) from the prospective Alpha Omega Cohort and Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study were included. Cox models were used to estimate categorical and continuous associations (using restricted cubic splines) of measured BMI and WC with all-cause and cardiovascular mortality risk, adjusting for age, sex, smoking, alcohol, physical activity and educational level. Analyses were repeated in subgroups of lifestyle factors (smoking, physical activity, diet quality), education and health determinants (diabetes, self-rated health). RESULTS: During ∼10 years of follow-up (91,947 person-years), 3,553 deaths occurred, including 1,620 from cardiovascular disease. U-shaped relationships were found for BMI and mortality risk, with the lowest risk for overweight patients (BMI ∼27 kg/m2). For obesity (BMI ≥30), the HR for all-cause mortality was 1.31 (95% CI: 1.11, 1.41) in male patients and 1.10 (95% CI: 0.92, 1.30) in female patients, compared to BMI 25-30 kg/m2. WC was also non-linearly associated with mortality, and HRs were 1.18 (95%CI:1.06, 1.30) in males and 1.31 (95%CI:1.05, 1.64) in females for the highest vs. middle category of WC. Results for cardiovascular mortality were mostly in line with the results for all-cause mortality. U-shaped associations were found in most subgroups, associations were moderately modified by physical activity, smoking and educational level. CONCLUSIONS: CAD patients with obesity and a large WC were at increased risk of long-term CVD and all-cause mortality, while mildly overweight patients had the lowest risk. These associations were consistent across subgroups of patients with different lifestyles and health status.

Improving obesity research: Unveiling metabolic pathways through a 3D In vitro model of adipocytes using 3T3-L1 cells.

Obesity, a burgeoning global health crisis, has tripled in prevalence over the past 45 years, necessitating innovative research methodologies. Adipocytes, which are responsible for energy storage, play a central role in obesity. However, most studies in this field rely on animal models or adipocyte monolayer cell cultures, which are limited in their ability to fully mimic the complex physiology of a living organism, or pose challenges in terms of cost, time consumption, and ethical considerations. These limitations prompt a shift towards alternative methodologies. In response, here we show a 3D in vitro model utilizing the 3T3-L1 cell line, aimed at faithfully replicating the metabolic intricacies of adipocytes in vivo. Using a workable cell line (3T3-L1), we produced adipocyte spheroids and differentiated them in presence and absence of TNF-α. Through a meticulous proteomic analysis, we compared the molecular profile of our adipose spheroids with that of adipose tissue from lean and obese C57BL/6J mice. This comparison demonstrated the model's efficacy in studying metabolic conditions, with TNF-α treated spheroids displaying a notable resemblance to obese white adipose tissue. Our findings underscore the model's simplicity, reproducibility, and cost-effectiveness, positioning it as a robust tool for authentically mimicking in vitro metabolic features of real adipose tissue. Notably, our model encapsulates key aspects of obesity, including insulin resistance and an obesity profile. This innovative approach has the potential to significantly impact the discovery of novel therapeutic interventions for metabolic syndrome and obesity. By providing a nuanced understanding of metabolic conditions, our 3D model stands as a transformative contribution to in vitro research, offering a pathway for the development of small molecules and biologics targeting these pervasive health issues in humans.

The association between caesarean section delivery and obesity at age 17 years. Evidence from a longitudinal cohort study in the United Kingdom.

BACKGROUND: Childhood and adolescent obesity are major, preventable public health concerns. Studies to date are inconclusive regarding an association between caesarean section (CS) delivery and offspring obesity, with fewer studies conducted in late adolescence. This study examined the association between CS delivery, with a specific focus on planned CS, and induction of labour and adolescent body mass index (BMI) and body fat percentage (BF%) at age 17 years. METHODS: Data on 8,880 mother-child pairs from the United Kingdom Millennium Cohort Study were analysed. The exposures were mode of delivery (normal vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS) and mode of delivery by induction of labour status. Crude and adjusted binary logistic regression and linear regression models were fitted examining BMI and BF% at age 17 years respectively, adjusting for several potential confounders. RESULTS: Adolescents born by CS did not have an elevated BMI or BF% compared to those born by normal VD. The fully adjusted results for overweight and obesity in children born by planned CS, compared to VD, were 1.05 (95% CI: 0.86-1.28) and 0.94 (95% CI: 0.72-1.23), respectively. The results were similar for the associations between CS and BF%, and between induction of labour and BMI. CONCLUSION: Overall, this large longitudinal study did not support an association between CS or induction of labour and overweight, obesity or BF%. It is possible that previously reported associations are due to residual or unmeasured confounding and/or underlying indications for CS delivery.

GLP-1-directed NMDA receptor antagonism for obesity treatment.

The N-methyl-D-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis1. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

[Analysis of weight loss, metabolism, and anti-reflux effect of sleeve gastrectomy combined with fundoplication as treatment of obesity complicated by gastroesophageal reflux disease].

Objective: To explore the weight-loss, metabolism, and anti-reflux effect of laparoscopic sleeve gastrectomy combined with fundoplication (SGFD) as treatment of obesity complicated by gastroesophageal reflux disease (GERD) with the aim of identifying the best treatment for such patients. Methods: This was a retrospective cohort study. Relevant clinical data of 140 patients with obesity (body mass index≥30 kg/m2) complicated by GERD (confirmed by preoperative GerdQ score, gastroscope, upper gastrointestinal radiography, 24-hour pH monitoring of esophagus, and high-resolution esophageal manometry) who had undergone bariatric surgery in the Minimally Invasive Surgery, Hernia and Abdominal Surgery Department of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2019 to February 2023 were collected. The participants were allocated to the following groups according to surgical procedure performed: sleeve gastrectomy group (SG group, 92 cases) versus SGFD (SGFD group, 48 cases). SGFD, a new type of anti-reflux weight loss surgery that achieves both anti-reflux and weight loss effects by a procedure involving "cutting first and then folding", was developed by our team. In this study, our main aim was to compare and analyze differences in outcomes between the SG and SGFD groups in terms of weight loss and improvements in metabolism and reflux 3 and 6 months postoperatively. Results: The 140 patients comprised 50 men and 90 women of average age 36.0±9.6 years and preoperative body mass index (BMI) (38.5±6.5) kg/m2. The average preoperative GERD score was 10.2±1.6. There were no significant differences in baseline characteristics between the SGFD and SG groups (all P>0.05). There were also no significant differences in postoperative hospital stay, intraoperative blood loss, or postoperative complications between the two groups (all P>0.05). However, the operation time was longer in the SGFD than SG group (137.5±10.5 minutes vs. 105.3±12.6 minutes, t=-15.131, P<0.001). Compared with preoperative values, fasting blood glucose, cholesterol, body mass, BMI, and GERD score were all lower 3 months postoperatively (all P<0.05). Six months postoperatively, triglyceride, uric acid, and DeMeester score were lower in the SGFD than SG group; however, the lower esophageal sphincter resting pressure was higher in the SGFD group (all P<0.05). There were no significant differences in weight loss indexes (body mass, BMI, percentage of excess body mass loss) or metabolic indexes (fasting blood glucose, triglyceride, cholesterol, and uric acid concentrations) between the SG and SGFD groups 3 and 6 months postoperatively (all P>0.05). However, anti-reflux indexes (GerdQ score, DeMeester score, and lower esophageal sphincter resting pressure) were all significantly better in the SGFD than SG group 6 months postoperatively (all P<0.05). Conclusion: Obese patients with GERD get good weight loss, metabolism improvement and anti-reflux effect after SGFD. SGFD is a safe and feasible surgical method, and its anti-reflux effect is better than SG at the 6th month after operation, so it is feasible.

A Paradigm Shift in Obesity Care.

Treatments are available and improving.

Weight Loss Medications: Stigma and Shortages.

Recently approved drugs offer hope and spark concern.