Severe Obesity Research Articles

Relationship Between Weight Loss, Changes in Serum hs-CRP Levels and apo A-1 Lipoprotein, and High-Density Lipoprotein-Cholesterol Ratios as Predictors for Improved Cardiovascular Risk Factors After Laparoscopic Sleeve Gastrectomy

IntroductionObesity, a major global health concern, is a known risk factor for cardiovascular disease (CVD), often due to dyslipidemia and insulin resistance. Laparoscopic sleeve gastrectomy (LSG) is an effective weight reduction surgery that not only alters body metabolism and gastrointestinal physiology but also significantly lowers cardiovascular disease risk.MethodsThis study explores the impact of weight loss on serum high-sensitivity C-reactive protein (hs-CRP), an established inflammatory marker, and changes in cardiovascular risk factors, particularly high-density lipoprotein-cholesterol (HDL-C) ratios, serum apo A-1, lipid profile, and HOMA-IR in severe obesity undergoing LSG. Anthropometric measurements and blood samples were collected preoperatively and 6 months postoperatively to hs-CRP, HOMA-IR, lipid profile, apo A-1, and low- and high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratios, total cholesterol to HDL-C (TC/HDL-C) ratio, and monocyte to high-density lipoprotein-cholesterol ratio (MHR).ResultsIn total, 70 patients were analyzed after 6 months and reached %TWL 27.4 ± 9.5 and %EWL 62.0 ± 15.4. Significant improvements were noted in all measured biomarkers. Analysis showed that each unit reduction in BMI significantly affected hs-CRP and HDL-C. Furthermore, moderate associations between hs-CRP and various cardiovascular disease risk biomarkers, including a negative correlation with apo A-1 and positive correlations with total cholesterol (TC), TC/HDL-C, and LDL-C/HDL-C, along with a mild positive correlation with HOMA-IR.ConclusionWeight loss following LSG significantly reduced inflammation and improved atheroprotection. Improved inflammation markers were associated with favorable changes in cardiovascular risk factors, including HDL-C ratios particularly TC/HDL-C, LDL-C/HDL-C, and apo A-1.Graphical

Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series

Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

Non-Invasive Assessment of Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents with Severe Obesity; Patient Characteristics and Association with Leptin-A Cross-Sectional Overview of Baseline Data from a RCT.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in adolescents with obesity. Nonetheless, the guidelines for screening and managing this disease are contradictory. The purpose of this study is to non-invasively assess the prevalence, patient characteristics, and potential associated factors of MASLD in this demographic. Methods: This study used baseline data from an RCT in adolescents eligible for bariatric surgery. MASLD was determined by measuring the hepatorenal index (HRI) with ultrasonography, blood liver tests, and the fatty liver index (FLI). Results: A total of 56 adolescents enrolled in the analyses; the majority were female n = 44 (79%); the mean age was 15.75 (±1.01) years; the average body mass index (BMI) was 44.08 (±5.16) kg/m2. In 35 (62.5%) of the patients, the HRI was abnormal. This group had a higher waist/hip ratio, elevated liver biochemistry, and significantly lower leptin levels (mean difference = -46.35, 95% CI -76.72, -15.99) compared to the group with a normal HRI. In 32 (55.2%) of the patients, ALT levels were elevated and the FLI was abnormal in all (100%) participants. Linear regression analysis indicated associations between the HRI and typical anthropometric and metabolic measurements; and an inverse association between HRI and leptin B = -0.003 (95% CI -0.005, -0.00), independently of sex- and age-adjusted BMI. Conclusions: MASLD is highly prevalent in adolescents with severe obesity. However, the prevalence strongly depends on which tool is used, namely the HRI (62.5%), alanine transaminase levels (55.2%), and FLI (100%). Our findings suggest that leptin may be a valuable biomarker in supporting the diagnosis of MASLD.

COMPARATIVE EFFECTIVENESS OF DIFFERENT BARIATRIC PROCEDURES ON WEIGHT LOSS AND COMORBIDITIES

Bariatric surgery has revolutionized the treatment of severe obesity, providing not only significant and sustained weight loss but also improvements in obesity-related comorbidities. Objective: The study's main objective is to compare the effectiveness of different bariatric procedures on weight loss and comorbidities. Methods: This retrospective cohort study was conducted at MTI Lady Reading Hospital Peshawar from 2019 to 2023. Data were collected from 91 patients who wanted weight loss. Participants aged >18 years, with a body mass index (BMI) of 40 or higher or a BMI of 35 or higher accompanied by significant obesity-related comorbidities such as type 2 diabetes, hypertension, or obstructive sleep apnea, were included in the study. All included patients underwent one of the four bariatric procedures. Results: The study included 91 patients who underwent various bariatric procedures at MTI Lady Reading Hospital between 2019 and 2023. The mean age of participants was 42.38 ± 2.35 years. The gender distribution comprised 55 females (60%) and 36 males (40%). The patients' mean preoperative body mass index (BMI) was 45.2 ± 3.01 kg/m². Biliopancreatic diversion with duodenal switch (BPD/DS) demonstrated the highest effectiveness, with an average %EWL of 78% at three years and the highest resolution rates for type 2 diabetes (95%), hypertension (90%), and obstructive sleep apnea (85%). Roux-en-Y gastric bypass (RYGB) also showed substantial weight loss and comorbidity resolution, achieving an average %EWL of 68% at three years. Conclusion: It is concluded that bariatric surgery is a highly effective intervention for achieving significant weight loss and resolving obesity-related comorbidities. Among the procedures studied, biliopancreatic diversion with duodenal switch (BPD/DS) demonstrated the highest effectiveness, with substantial weight loss and resolution rates for type 2 diabetes, hypertension, and obstructive sleep apnea.

The Impact of Bariatric Surgery on Glutathione Synthesis in Individuals with Severe Obesity.

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4-123.7) vs. 76.9 (49.3-110.1) % pool/day, p = 0.58] or absolute synthesis rate [1.85 (1.25-3.32) vs. 1.92 (1.43-3.03) mmol/L RBC/day, p = 0.97]. Despite a post-surgery increase in glycine concentration, no statistically significant changes in RBC GSH concentration or synthesis rates were detected. Further, the significant correlation between plasma glycine and RBC GSH concentration at baseline (r = 0.46, p < 0.01) was also lost following bariatric surgery. GSH concentration was significantly lower in participants with obesity, but bariatric surgery did not significantly increase GSH concentrations or synthesis rates.

Type 2 diabetes: a sacrifice program handling energy surplus

Abstract Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss. The body employs three adaptive strategies in response to energy surplus: the first one is adipose tissue expansion to store the energy for weight gain under normal weight conditions; the second one is insulin resistance to slow down adipose tissue expansion and weight gain under overweight conditions; and the third one is the onset of T2DM following β cell failure to reverse the weight gain in obese conditions. The primary signaling molecules driving the compensatory responses are adenosine derivatives, such as adenosine triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), and reduced nicotinamide adenine dinucleotide (NADH). These molecules exert their effects through allosteric, post-translational, and transcriptional regulation of metabolic pathways. The insights suggest that insulin resistance and T2DM are protective mechanisms in the defense against excessive adiposity to avert severe obesity. The perspective provides a unified framework explaining the interactions between the two diseases and opens new avenues in the study of T2DM.

Home environment factors associated with child BMI changes during COVID-19 pandemic

BackgroundThe influence of home obesogenic environments, as assessed by the validated Family Nutrition and Physical Activity (FNPA) tool, and child obesity during the COVID pandemic were evaluated using electronic health records in this retrospective cohort study.MethodsHistorical data on BMI and the FNPA screening tool were obtained from annual well-child visits within the Geisinger Health System. The study examined youth ages 2–17 that had a BMI record and an FNPA assessment prior to the pandemic (BMI 3/1/19–2/29/20), 1 BMI record 3 months into the pandemic (6/1/20–12/31/20) and 1 BMI in the second year of the pandemic (1/1/21–12/31/21). Tertiles of obesity risk by FNPA score were examined. Mixed-effects linear regression was used to examine change in BMI slope (kg/m2 per month) pre-pandemic to pandemic using FNPA summary and subscales scores as predictors and adjusting for confounding factors.ResultsThe analyses included 6,746 children (males: 51.7%, non-Hispanic white: 86.6%, overweight:14.8%, obesity:10.3%, severe obesity: 3.9%; mean(SD) age: 5.7(2.8) years). The rate of BMI change in BMI was greatest from early pandemic compared to pre-pandemic for children in lowest versus highest tertiles of FNPA summary score (0.079 vs. 0.044 kg/m2), FNPA-Eating (0.068 vs. 0.049 kg/m2), and FNPA-Activity (0.078 vs. 0.052 kg/m2). FNPA summary score was significantly associated with change in BMI from the pre-pandemic to early pandemic period (p = 0.014), but not associated with change in BMI during the later pandemic period.ConclusionsThis study provides additional insight into the changes in the rate of BMI change observed among children and adolescents in the United States during the COVID-19 pandemic. The FNPA provides ample opportunity to continue our exploration of the negative impact of the COVID-19 pandemic on the longitudinal growth patterns among children and adolescents.

Severe obesity among patients with left ventricular assist devices

Patients with obesity and advanced heart failure requiring left ventricular assist device (LVAD) support are more likely to experience LVAD complications and may be disproportionately Black and/or female when compared to patients without obesity. Among these patients, obesity may represent a barrier to transplant eligibility and a marker of inequity in heart transplantation and health outcomes in advanced heart failure. To better understand this issue at our institution, we examined our active LVAD cohort and found that almost one-third of all patients had severe obesity with BMI ≥ 35 kg/m2. Patients with LVADs and severe obesity were significantly younger and more likely to self-identify as Black, and numerically more likely to be female. Weight management in this group represents a vital area for improved equity in health outcomes and barriers to heart transplantation. NA.

Long-Term Effectiveness and Outcomes of Bariatric Surgery: A Comprehensive Review of Current Evidence and Emerging Trends.

Obesity is a global epidemic associated with an increased risk of severe health conditions such as type 2 diabetes, cardiovascular diseases, and certain cancers. Bariatric surgery has become a pivotal treatment for severe obesity, offering significant improvements in weight loss and comorbidity resolution. This comprehensive review aims to assess the long-term effectiveness and outcomes of various bariatric surgical procedures, highlighting current evidence and emerging trends in the field. We extensively reviewed the literature, including randomized controlled trials, cohort studies, and meta-analyses, to evaluate long-term weight loss, resolution of obesity-related comorbidities, quality of life (QoL), and complications associated with different bariatric procedures. Bariatric surgery has demonstrated substantial and sustained weight loss over the long term, with varying degrees of effectiveness among different procedures. Gastric bypass and sleeve gastrectomy are associated with significant improvements in comorbidities such as type 2 diabetes and hypertension. QoL outcomes are generally positive, improving physical health, mental well-being, and social functioning. However, long-term complications, including nutritional deficiencies and the need for reoperations, remain challenges. Emerging trends such as minimally invasive techniques and nonsurgical interventions show promise in enhancing patient outcomes. Bariatric surgery remains a highly effective intervention for managing severe obesity and its related health issues. While long-term outcomes are generally favorable, continued advancements in surgical techniques and postoperative care are crucial for optimizing results and minimizing complications. Future research should focus on personalized approaches to patient management and the development of novel treatment modalities to further improve outcomes in the long term.

The Efficacy of Roux-en-Y Gastric Bypass in Young-Onset Diabetes Mellitus: A Narrative Review.

Type 2 diabetes mellitus (T2DM) in youth is invading the communities because, if not controlled on time, the long-term complications include cardiovascular diseases, nephropathy, neuropathy, and retinopathy that cause immense mortality and morbidity. Lifestyle changes and antidiabetic drugs are considered the foundation of T2DM therapy. However, these adjustments usually do not effectively produce long-term glycemic regulation, especially in patients with obesity of the third and fourth degrees. Bariatric surgery has also been identified as an efficacious intervention for obesity and obesity-related complications such as T2DM. Roux-en-Y gastric bypass (RYGB) has proven to be one of the most effective procedures in causing considerable weight loss and enhancing glycemic changes. This review provides a comprehensive analysis of RYGB in patients with young-onset T2DM regarding the improvement of glycemic control, weight loss, and diabetes comorbidities. RYGB has been established as a practice in the treatment of T2DM and severe obesity. This narrative review underscores the various effects of RYGB, such as enhanced glycemic control, considerable and long-term weight loss, and reduced cardiovascular disease risks. However, the review also points toward the directions and the adverse effects of RYGB regarding metabolic and skeletal health. There are risks of nutritional deficiencies, increased fracture rates, and even relapse to diabetes, which make patient selection, proper pre and postoperative investigation, and critical monitoring.

Pediatric metabolic and bariatric surgery: indications and preoperative multidisciplinary evaluation

The standard of care for pediatric patients with severe obesity considering metabolic and bariatric surgery is a preoperative multidisciplinary evaluation. A multidisciplinary team allows for the efficient use of variable personnel expertise to evaluate, manage, and support a pediatric patient and family through metabolic and bariatric surgery. This review discusses the purpose, recommended team members, patient selection, content, and benefits of the multidisciplinary preoperative evaluation. This evaluation should reduce barriers to care and optimize patient safety and outcomes while taking into consideration the unique developmental needs of this age group.

Gestational Weight Gain Following Metabolic Bariatric Surgery: A Scoping Review.

Metabolic bariatric surgery remains the most effective and durable treatment for severe obesity. Women of reproductive age represent the largest demographic group undergoing these procedures. Metabolic bariatric surgery can have both beneficial and adverse effects on pregnancy outcomes. One of the most common adverse effects is fetal growth restriction. To mitigate these adverse effects, it is crucial to explore lifestyle modifications aimed at promoting a healthy pregnancy. Modifiable factors during pregnancy after metabolic bariatric surgery include the amount of gestational weight gain. The aim of this comprehensive review is to provide an overview of what is known about gestational weight gain in pregnancy after bariatric metabolic surgery. This review is focused on the two most performed procedures: sleeve gastrectomy and Roux-en-Y gastric bypass.

Characteristics Associated With Abnormal Dynamic Flow in Patients With Severe Obesity Undergoing PET Myocardial Perfusion Imaging

Characteristics Associated With Abnormal Dynamic Flow in Patients With Severe Obesity Undergoing PET Myocardial Perfusion Imaging

72269 - Ten-year results after primary gastric bypass for severe obesity: results from the Scandinavian Obesity Registry (SOReg)

72269 - Ten-year results after primary gastric bypass for severe obesity: results from the Scandinavian Obesity Registry (SOReg)

Assessing the Prevalence of Male Obesity-Associated Gonadal Dysfunction in Severe Obesity: A Focus on the Impact of Bariatric Surgery and Surgical Approaches

PurposeObesity is an important risk factor for secondary hypogonadism in men. Several studies evaluated the impact of bariatric surgery on gonadal function in men, proving an improvement in testosterone levels, without yet a global consensus on the impact of different surgical approaches. Objectives of the study are: to estimate the prevalence of obesity-associated gonadal dysfunction among men with severe obesity; to evaluate the response to bariatric surgery in terms of resolution of this condition, distinguishing between restrictive and restrictive-malabsorptive surgery.MethodsWe conducted a retrospective evaluation of 413 males with severe obesity (BMI 44.7 ± 8.3 kg/m2). A subgroup of them (61.7%) underwent bariatric surgery. Anthropometric assessment (weight, BMI, waist and hip circumference), metabolic (glyco-lipidic asset and urate) and hormonal (morning gonadotropin and total testosterone) assessments were carried out at baseline and 3–6 months post-surgery.ResultsUsing a TT threshold of 2.64 ng/ml, 256 out of 413 (62%) patients were categorized as having biochemical hypogonadism. At multivariate analysis, the only parameter significantly associated with biochemical hypogonadism, was BMI value (p = 0.001). At 3–6 months after surgery, during the acute weight loss phase, only 20.1% of patients still had biochemical hypogonadism. At multivariate analysis, which included age, presurgical BMI, pre-surgical TT, surgical approach and %EWL, presurgical TT levels (p = 0.0004), %EWL (p = 0.04), and mixed restrictive-malabsorptive surgery (p = 0.01), were independently associated with the recovery of gonadal function.ConclusionsThe results of this study underscore the potential reversibility of obesity-associated gonadal dysfunction through bariatric surgery, highlighting the importance of considering surgical approach.Graphical

A pediatric primary care practice-based obesity intervention to support families: a cluster-randomized clinical trial.

The American Academy of Pediatrics recommends that pediatric practices help families make lifestyle changes to improve BMI, but provider time and access to treatment are limited. This study compared the effectiveness of two pediatric practice-based referral interventions in reducing BMI. In this cluster-randomized clinical trial, 20 pediatric primary care practices were randomized to telephonic coaching (Fitline Coaching) or mailed workbook (Fitline Workbook). Parents and their 8- to 12-year-old children with BMI ≥ 85th percentile completed assessments at baseline and at6 and 12 months post baseline. Primary outcomes were 12-month BMI percentile and z score. A total of 501 children and their parents received Fitline Coaching (n = 243) or Fitline Workbook (n = 258); 26.8% had overweight, 55.4% had obesity, and 17.8% had severe obesity. Mean (SD) age was 10.5 (1.4), and 47.5% were female. BMI percentile improved in both groups; 12-month decline in continuous BMI z score was not statistically significant in either group. However, 20.8% of telephonic coaching participants and 12.4% of workbook participants achieved a clinically significant reduction of at least 0.25 in BMI z score, a significant between-group difference (p = 0.0415). Both low-intensity interventions were acceptable and produced modest improvements in BMI percentile. One in five children in the telephonic coaching condition achieved clinically meaningful BMI z score improvements. However, more research is needed before such a program could be recommended for pediatric primary care practice.

Robotic sleeve gastrectomy through medial approach for severe obesity: Safe introduction, technical description and case series.

The use of robotic surgery has increased worldwide and has the potential to amplify the surgeon's skill owing to its versatile functions. However, robotic surgery requires specific skills that differ from laparoscopic surgery, and the field of robotic surgery training systems is underdeveloped. Therefore, to ensure patient safety, a task protocol should be prepared before the introduction of novel robotic surgeries. This article provides the pioneering description of performing robotic sleeve gastrectomy (RSG) through the medial-to-lateral approach, utilising our newly revised protocol. The preliminary clinical results of 10 patients who underwent RSG using the stapling-first technique between June 2021 and March 2023 showed that RSG is safe and feasible and that the implementation of a task protocol is an effective strategy for the safe introduction of a novel robotic surgical technique.

Sociodemographic and Lifestyle Factors and Epigenetic Aging in US Young Adults

Epigenetic clocks represent molecular evidence of disease risk and aging processes and have been used to identify how social and lifestyle characteristics are associated with accelerated biological aging. However, most research is based on samples of older adults who already have measurable chronic disease. To investigate whether and how sociodemographic and lifestyle characteristics are associated with biological aging in a younger adult sample across a wide array of epigenetic clock measures. This cohort study was conducted using data from the National Longitudinal Study of Adolescent to Adult Health, a US representative cohort of adolescents in grades 7 to 12 in 1994 followed up for 25 years to 2018 over 5 interview waves. Participants who provided blood samples at wave V (2016-2018) were analyzed, with samples tested for DNA methylation (DNAm) in 2021 to 2024. Data were analyzed from February 2023 to May 2024. Sociodemographic (sex, race and ethnicity, immigrant status, socioeconomic status, and geographic location) and lifestyle (obesity status by body mass index [BMI] in categories of reference range or underweight [<25], overweight [25 to <30], obesity [30 to <40], and severe obesity [≥40]; exercise level; tobacco use; and alcohol use) characteristics were assessed. Biological aging assessed from banked blood DNAm using 16 epigenetic clocks. Data were analyzed from 4237 participants (mean [SD] age, 38.4 [2.0] years; percentage [SE], 51.3% [0.01] female and 48.7% [0.01] male; percentage [SE], 2.7% [<0.01] Asian or Pacific Islander, 16.7% [0.02] Black, 8.7% [0.01] Hispanic, and 71.0% [0.03] White). Sociodemographic and lifestyle factors were more often associated with biological aging in clocks trained to estimate morbidity and mortality (eg, PhenoAge, GrimAge, and DunedinPACE) than clocks trained to estimate chronological age (eg, Horvath). For example, the β for an annual income less than $25 000 vs $100 000 or more was 1.99 years (95% CI, 0.45 to 3.52 years) for PhenoAgeAA, 1.70 years (95% CI, 0.68 to 2.72 years) for GrimAgeAA, 0.33 SD (95% CI, 0.17 to 0.48 SD) for DunedinPACE, and -0.17 years (95% CI, -1.08 to 0.74 years) for Horvath1AA. Lower education, lower income, higher obesity levels, no exercise, and tobacco use were associated with faster biological aging across several clocks; associations with GrimAge were particularly robust (no college vs college or higher: β = 2.63 years; 95% CI, 1.67-3.58 years; lower vs higher annual income: <$25 000 vs ≥$100 000: β = 1.70 years; 95% CI, 0.68-2.72 years; severe obesity vs no obesity: β = 1.57 years; 95% CI, 0.51-2.63 years; no weekly exercise vs ≥5 bouts/week: β = 1.33 years; 95% CI, 0.67-1.99 years; current vs no smoking: β = 7.16 years; 95% CI, 6.25-8.07 years). This study found that important social and lifestyle factors were associated with biological aging in a nationally representative cohort of younger adults. These findings suggest that molecular processes underlying disease risk may be identified in adults entering midlife before disease is manifest and inform interventions aimed at reducing social inequalities in heathy aging and longevity.

Time-restricted eating affects human adipose tissue fat mobilization.

Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures. Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting. TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001). This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.

Myocardial ultrastructure of human heart failure with preserved ejection fraction.

Over half of patients with heart failure have a preserved ejection fraction (>50%, called HFpEF), a syndrome with substantial morbidity/mortality and few effective therapies1. Its dominant comorbidity is now obesity, which worsens disease and prognosis1-3. Myocardial data from patients with morbid obesity and HFpEF show depressed myocyte calcium-stimulated tension4 and disrupted gene expression of mitochondrial and lipid metabolic pathways5,6, abnormalities shared by human HF with a reduced EF but less so in HFpEF without severe obesity. The impact of severe obesity on human HFpEF myocardial ultrastructure remains unexplored. Here we assessed the myocardial ultrastructure in septal biopsies from patients with HFpEF using transmission electron microscopy. We observed sarcomere disruption and sarcolysis, mitochondrial swelling with cristae separation and dissolution and lipid droplet accumulation that was more prominent in the most obese patients with HFpEF and not dependent on comorbid diabetes. Myocardial proteomics revealed associated reduction in fatty acid uptake, processing and oxidation and mitochondrial respiration proteins, particularly in very obese patients with HFpEF.