Obesity Syndrome Research Articles

Effect of a Multifactorial Weight Loss Intervention on HDL Cholesterol Efflux Capacity and Immunosenescence: A Randomized Controlled Trial

Objective Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. Method CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. Results Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (−3.32% ± 12.54% and −6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. Conclusions A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

7529 A Silent Menace Of Mounjaro: Acute Renal Failure Associated With Tirzepatide

Abstract Disclosure: F. farhat: None. P. Gonzalez: None. A.B. Ravin: None. F.F. Foo: None. S. Patel: None. J. Cheng: None. S.W. Holland: None. A. Chinnici: None. A. Abu Homoud: None. Introduction: Obesity and metabolic syndrome are serious conditions resulting in high morbidity and mortality. Approximately 70% of Americans suffer from obesity. In light of increasing obesity rates, many new medications, including GLP1 receptor agonists, have been approved by the FDA. Tirzepatide injection, known as Mounjaro, is a new medication for diabetes mellitus which offers additional benefits of weight loss. Mounjaro’s side effects can range from mild symptoms including nausea, vomiting, and diarrhea, to more severe symptoms like pancreatitis, and allergic reaction. In this report we present a rare case of renal failure after initiation of Mounjaro. Case presentation:This is a 59 year old male with past medical history significant for hypertension, dysglycemia who presented to the Emergency Department (ED) after two near syncopal events. He was started on Mounjaro a month ago. One week prior to presentation, the patient received his 6th dose of Mounjaro and shortly after he began experiencing generalized weakness associated with nausea, vomiting, diarrhea, and lower extremity cramps. His symptoms continued to worsen which prompted him to come to the hospital. Moreover, he had not voided in 4 days. In the ED, he was severely hyponatremic and AKI with a sodium of 115 and creatinine of 6.62.Patient was admitted to the ICU for further treatment and monitoring. He was evaluated by a nephrologist and determined that dialysis was not necessary as his AKI was resultant from volume depletion due to severe diarrhea as creatinine improved to 3.89 after resuscitation. He was discharged with no further complications.Discussion:This case report brings attention to a potential serious adverse effect from the use of a GLP1, Mounjaro, that has not been described before. Previous reports have described AKI caused by GLP1 treatment but none to our knowledge have discussed renal failure in patients without underlying renal disease. Patients with Chronic Kidney Disease and use of medications such as NSAIDs, diuretics, or angiotensin receptor blockers are more likely to develop renal complications.Mounjaro and other GLP1 medications have gained popularity among patients as they are effective in weight loss and simple to administer.. Additionally, more practitioners are now prescribing these medications for diabetics as they offer a more favorable safety profile compared to other available medications. Although GI side effects are well known, patients should be warned about the potential of severe dehydration leading to renal complications. Conclusion: Mounjaro has been associated with gastrointestinal adverse effects which include nausea, vomiting and diarrhea, and if severe, can lead to AKI and possible renal failure even without underlying renal disease. Monitoring renal functions after initiating or escalating the dose of Mounjaro should be a routine workup by all providers. Presentation: 6/2/2024

7190 Serum uric acid and serum uric acid-to-creatinine ratio and its association with metabolic syndrome in Korean adolescents: the nation-wide population-based study

Abstract Disclosure: S. Jung: None. J. Kim: None. S. Kim: None. Backgrounds: As the prevalence of obesity and metabolic syndrome (MetS) among the pediatric population continues to rise, it is crucial to identify the factors associated with cardiometabolic risk factors (CMRFs) to prevent the future development of diabetes and cardiovascular disease. Elevated serum uric acid (SUA) and SUA-to-creatine ratio (SUA/Cr) levels are associated with MetS, CMRFs, and non-alcoholic fatty liver disease (NAFLD) in adults. However, studies on the usefulness of SUA or SUA/Cr to predict MetS in adolescents were sparse. The aim of this study is to investigate the association between SUA or SUA/Cr level and MetS and CMRFs among Korean adolescents. Material/Methods: Data collected from the Korea National Health and Nutrition Examination Survey between 2016 and 2021, which was nationally representative cross-sectional data, were used. A total of 2,218 subjects (1,185 males, 54.0%) aged 13-18 years were included in this study. They were classified into tertiles of SUA or SUA/Cr levels (T1, lower tertile; T2, mid-tertile; and T3, upper tertile) according to sex. The prevalence of MetS and CMRFs, including alanine aminotransferase (ALT), was compared by tertiles of SUA. Results: The mean SUA and SUA/Cr was higher in males than females (6.37 ± 0.04 mg/dL and 4.66 ± 0.06 mg/dL, P &amp;lt; 0.001 for SUA; 7.90 ± 0.07 mg/dL and 7.30 ± 0.06 mg/dL, P &amp;lt; 0.001 for SUA/Cr). Z-scores of body mass index, waist circumference, waist-height ratio, levels of total cholesterol, triglyceride, and ALT were significantly higher in T3 of SUA and SUA/Cr in both sexes, while high-density lipoprotein cholesterol (HDL-C) was lower. In T3 of SUA and SUA/Cr, the prevalence and odds ratio (95% confidence interval) increased significantly in abdominal obesity [34.5%, 5.5 (4.0, 7.7) vs. 31.3%, 5.3 (3.7, 7.6)], elevated blood pressure [19.5%, 2.1 (1.5, 2.9) vs. 16.3% 1.6 (1.1, 2.2)], elevated triglyceride [29.5%, 2.1 (1.5, 2.8) vs. 27.9%, 2.1 (1.6, 2.8)], low HDL-C [22.5%, 3.4 (2.4, 5.0) vs. 20.2%, 2.6 (1.8, 3.9)], elevated ALT [31.5%, 5.7 (3.8, 8.6) vs. 19.1% 4.9 (3.2, 7.6)], obesity [33.6%, 7.6 (5.2, 11.2) vs. 25.9%, 6.0 (3.9, 9.1)] and MetS [13.7%, 7.4 (4.3, 13.0) vs. 10.8%, 6.8 (3.9, 9.1)], compared with T1 of SUA and SUA/Cr, respectively. In the receiver operating characteristic curve analysis, the area under the curve of predicting MetS was 0.681 for males and 0.823 for females using SUA and 0.653 for males and 0.840 for females using SUA/Cr. The proportion of participants with ≥ 3 CMRFs was 2.1% in T1, 3.5% in T2, and 13.7% in T3 in SUA (P &amp;lt; 0.001) and 2.1% in T1, 5.8% in T2, and 10.8% in T3 in SUA/Cr (P &amp;lt; 0.001). Conclusions: In this nationwide cross-sectional study, SUA and SUA/Cr levels are associated with MetS, its components, and the marker of NAFLD in Korean adolescents. SUA and SUA/Cr seem to be more specific in diagnosing MetS in female adolescents. Both SUA and SUA/Cr could be used as important markers to predict MetS in adolescents. Presentation: 6/1/2024

7299 An Eucaloric High-Fat Diet Suppresses Urinary Estrogen and Progesterone Metabolites, Mimicking Reprometabolic Syndrome in Normal Weight Women

Abstract Disclosure: K. Kuhn: None. A.P. Bradford: Consulting Fee; Self; Amazon. N.F. Santoro: Advisory Board Member; Self; Menogenix, Astellas, Que Oncology, Amazon. Consulting Fee; Self; Ansh. Introduction: Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. We employed a eucaloric, high-fat diet (HFD) to attempt to reproduce the decreased urinary estrogen and progesterone metabolites, characteristic of this phenotype, in healthy women of normal BMI. Materials and Methods: 18 women with normal BMI (18-24.9kg/m²), mean age 29.1±6.3, were recruited for a four-month study including a prescribed 30-day, eucaloric, high-fat, dietary intervention (48% calories from fat). Women collected daily morning urine for 4 menstrual cycles. Daily urinary estrone conjugate (E1c) and pregnanediol-3-glucuronide (Pdg) levels were measured by immunoassay before, during and after the HFD. Paired t tests were used to compare average urinary E1c and Pdg levels and area under the curve (AUC) to determine the impact of the HFD. Cycles were aligned by LH peak (day 0). Results: Participants were weight stable throughout the 4 month study period with no change in BMI (pre-diet BMI 21.46±1.95 kg/m2 and post-diet BMI 21.35±1.81 kg/m2). Average mid cycle E1c peak was significantly lower during (32.4 ng/mg creatinine) and after the HFD (26.5 ng/mg creatinine), compared to pre-diet levels (43.2 ng/mg creatinine; p&amp;lt; 0.001). Post-diet urinary Pdg (AUC) was also significantly lower than pre-diet (p&amp;lt; 0.01). Follicular (days -14 to 0) and luteal phase (days 2-14) E1c AUC was significantly decreased post HFD (p&amp;lt; 0.05). Follicular and luteal phase Pdg levels were also significantly decreased post HFD (p&amp;lt;0.001, both). No significant changes in menstrual cycle length were observed throughout the study. Conclusion: Consumption of a high-fat diet for one month was sufficient to induce a significant reduction in E1c and Pdg, characteristic of Reprometabolic Syndrome of obesity, in normal weight, eumenorrheic women. This finding provides important insights regarding the mechanisms underlying reproductive dysfunction in obesity and indicates that a dietary intervention may be an effective strategy to mitigate sub-optimal reproductive hormone levels in women with obesity-related subfertility. Presentation: 6/1/2024

Causal Relationship Between Childhood Obesity and Sleep Apnea Syndrome: Bidirectional Two-Sample Mendelian Randomization Analysis.

Childhood obesity has become a global pandemic, leading to a range of diseases. Childhood obesity appears to be associated with an increased prevalence of sleep apnea syndrome. Sleep apnea is an inestimable risk factor for thrombosis, hypertension, cardiomyopathy and many other diseases. Therefore, exploring the relationship between childhood obesity and sleep apnea syndrome will help to understand the potential link between the two and provide research directions for future disease prevention and treatment. However, no studies have confirmed whether there is a causal relationship between childhood obesity and sleep apnea syndrome. The IEU OpenGWAS project provided the GWAS-aggregated data for childhood obesity and sleep apnea syndrome. Inverse-variance weighted (IVW) was used as the main method to evaluate the causal relationship between childhood obesity and sleep apnea syndrome. Single nucleotide polymorphisms (SNPs) were regarded as instrumental variables, and the screening threshold was P <5.0×10-6. Leave-one-out method was performed to confirm the robustness of the results. IVW analysis confirmed a causal relationship between genetic susceptibility to childhood obesity and an increased risk of sleep apnea syndrome [odds ratio (OR)=1.12, 95% confidence interval (CI): 1.02-1.23, P=0.016]. However, two-sample MR results also showed no causal relationship between genetic susceptibility to sleep apnea syndrome and an increased risk of childhood obesity (OR=1.50, 95% CI: 0.95-2.38, P=0.083). The intercept of MR-Egger regression was close to 0, which implies that there are no confounding factors in the analysis to affect the results of two-sample MR analysis. The leave-one-out results show that the bidirectional two-sample MR analysis results were robust. There is a causal relationship between genetic susceptibility to childhood obesity and increased risk of sleep apnea syndrome. People with a history of childhood obesity should pay more attention to physical examination to early prevention and management of sleep apnea syndrome.

Intestinal epithelial cell NCoR deficiency ameliorates obesity and metabolic syndrome

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Metabolic Syndrome and Cardiovascular Risk Factors in a Fishing Community in Southern Italy

BackgroundWork organization and psychosocial factors influencing sleep patterns may be significant risk factors for developing obesity and metabolic syndrome (MetS). However, the impact on the health of working patterns in the fishing sector is not well characterized. The aim of the study is to determine the prevalence of MetS and its components in fishermen and to analyze occupational-specific risk factors contributing to metabolic alterations. MethodsOne hundred forty-three male fishermen from Apulia (Southern Italy) and 93 male university workers age-matched and from the same geographical area were included in this cross-sectional study. A questionnaire was administered to investigate socio-demographic variables, work activity, health status, and dietary habits. All subjects underwent clinical evaluation and blood sampling to depict their metabolic profile. ResultsA higher body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (p < 0.001) were observed in fishermen than in university workers. No significant difference between the two groups was observed in the prevalence of MetS (15.4% fishermen vs 16.1% university workers) and its relevant diagnostic criteria, except abdominal obesity (42.7% fishermen vs 29.0% university workers, p = 0.021). The Castelli risk index, the monocyte/c-HDL ratio, and the Sokolow index were significantly greater in fishermen (p < 0.001). In the fishermen group, the total number of sleeping hours on working days was negatively correlated with WC (r = -0.17; p = 0.04), low-density lipoprotein cholesterol (c-LDL) (r = -0.21; p = 0.02), and the homeostasis model assessment (HOMA) index (r = -0.19; p = 0.02). ConclusionThe higher prevalence of obesity and the imbalance of the metabolic profile observed in fishermen could be related to occupational factors, including the specific working pattern that influences their sleeping hours and sleeping-waking rhythms.

Physical Fitness Modulates The Relationship Between Abdominal Obesity And Metabolic Syndrome In Elderly Korean Women

Physical Fitness Modulates The Relationship Between Abdominal Obesity And Metabolic Syndrome In Elderly Korean Women

Should Gallbladder Pathologies Be Investigated in Patients With Colon Polyps?

Background Data regarding the frequency of development of gallbladder pathologies in patients with colon polyps are quite limited and heterogeneous. Hence, this study aimed to investigate whether colon polyps cause an increased risk of developing gallbladder pathologies and the necessity of ultrasonographic screening. Methodology This retrospective, cross-sectional study was conducted among adult patients who underwent a colonoscopy and hepatobiliary ultrasound as part of their health check-up from January 2018to January 2023. The frequency, etiological factors, and association of gallbladder pathologies with colon polyps were investigated. Results A total of 128 patients were included in the study. When the distribution of colon polyp pathology was examined, 78.9% (n = 101) were adenomas, 18.8% (n = 24) were non-neoplastic polyps, and 2.3% (n = 3) were adenocarcinomas. The rate of patients with gallbladder stones was 10.9% (n = 14) and the rate of patients with polyps was 18.8% (n = 24). On multivariate logistic regression analysis, variables found to be significant for the development of gallbladder pathologies were determined as obesity, hyperlipidemia, and polyp's distal colon location. Conclusions Obesity and metabolic syndrome were among the etiological factors in this patient group. Hepatobiliary ultrasound, a non-invasive and inexpensive examination, is useful in patients with colon polyps.

In vivo imaging of alkaline phosphatase in lipid metabolic diseases with a photoacoustic probe

Lipid metabolic diseases have become an important challenge to global public health. Along with lifestyle changes, the incidence of obesity, diabetes and other metabolic syndromes is on the rise, and the number of patients with fatty liver disease is also increasing. Therefore, it is particularly important to develop effective lipid imaging strategies to monitor and manage fatty liver disease. Herein, based on the essential role of alkaline phosphatase (ALP) in both AS and OB, in vivo imaging of ALP was achieved in two lipid metabolic diseases models with a photoacoustic (PA) probe phosphorylated hemicyanine (P-Hcy). After being triggered by ALP, P-Hcy responded in different modalities including absorbance, fluorescence and, most significantly, PA-reporting. Notably, the PA signal showed the reliable linear correlation to the ALP level within the range of 0–800 U/L. The probe P-Hcy exhibited the advantages including high sensitivity, high selectivity, and steadiness in required biological conditions. The intracellular imaging results ensured that P-Hcy could visualize the ALP level in the foam cells induced from mouse mononuclear macrophages. In the healthy and lipid metabolic diseases models, P-Hcy was able to distinguish well between a lipid metabolic disease model and a healthy mouse model by photoacoustic imaging. By combining the ALP detection with P-Hcy in PA/fluorescence modality and traditional techniques such as blood biochemical testing and immunohistochemically staining, more potential strategy to accurately diagnose lipid metabolic diseases in the pre-clinical trials might be developed in future.

Nutritional Aspects of Spina Bifida Care: Optimizing Medical Management and Surgical Healing.

This review aims to highlight background of contributing factors for suboptimal nutrition in individuals with spina bifida and introduce strategies for amelioration. Recent studies demonstrate increased risk of metabolic syndrome by neurosegmental level, which is associated with truncal obesity and reduced mobility. From the neonatal intensive care stay, which may disrupt breast feeding and the developing microbiome of the gastrointestinal tract, to early childhood various insults may lead to suboptimal feeding practices, preferences and dietary intake. Family coping skills, financial stressors may lead to food insecurity and/or residence in an area with limited availability of fresh food. As children grow, weakness and challenging transfers may lead to more sedentary lifestyle and weight gain despite limited linear growth. Body habitus changes including atrophy of the lower extremities may lead to decreased muscle mass and reduced energy expenditure, with predisposition to truncal obesity and metabolic syndrome.

Obesity in patients with craniopharyngioma in the South Asian region – A distinct phenotype

BackgroundCraniopharyngiomas are rare benign tumors located in the sellar and suprasellar region, with an incidence of 0.5–2 cases per million as reported in Western studies. Post-treatment, including surgery and/or radiotherapy, many patients develop significant obesity, primarily due to hypothalamic damage and associated complications such as hypopituitarism. In the South Asian population, genetic predisposition to obesity at lower BMIs, coupled with a carbohydrate-rich diet, may exacerbate obesity in craniopharyngioma patients, presenting a unique challenge. MethodsThis submission is a commentary based on a comprehensive literature review. The authors conducted the review using PubMed to focus on English-language articles covering hypothalamic obesity, craniopharyngioma and obesity in the South Asian population from 1939 to the present. ResultsThe literature review revealed that 50–60 % of patients treated for craniopharyngioma develop obesity, predominantly linked to hypothalamic damage, although these data are mainly derived from Western studies. Hypopituitarism was frequently observed, further contributing to the obesity. Despite a caloric intake appropriate for the age and gender, these patients exhibited reduced physical activity as measured by wrist accelerometers. Patients with hypothalamic obesity due to craniopharyngioma are at risk for metabolic syndrome and cardiovascular morbidity. Additionally, visual impairment was common, leading to a decreased quality of life. The South Asian population, genetically predisposed to visceral obesity and a carbohydrate-rich diet, may display a distinct phenotype. Although multiple treatment modalities have been tried, there is no definite treatment modality available to counteract this condition at present. ConclusionSouth Asian phenotype of craniopharyngioma-related obesity is characterized by significant metabolic and hormonal dysregulation, influenced by both dietary and genetic factors. Nevertheless, there may be a lot to be still understood about this devastating, rapid, relentless hypothalamic obesity syndrome. Also, a higher morbidity rate within this population, underscores the need for further research to develop targeted interventions.

CANVAS For A Diagnosis: Can You Hear The Hooves Of Zebras?

Abstract Background A 75year old male presented to a Movement Disorder Service with complex multimorbidity including: chronic pain, type 2 diabetes mellitus, hypoventilatory obesity syndrome, biliary calculus, moderate aortic stenosis, marked orthostatic hypotension, pulmonary hypertension, coronary artery bypass grafting, permanent pacemaker for complete atrioventricular block, carpal tunnel release bilaterally, polypharmacy and bilateral cataracts. History elucidated a distal to proximal sensory loss over 20years and neuropathic pain without nerve conduction confirmation; and progressively ataxic gait over several years. He also complained of hypophonia, bruxism, excessive daytime somnolence, passages, transitions, visual agnosia, textural illusion, oscillopsia, irritability, inflexibility, hoarding, impulsivity, disorganisation, inattention, apathy, depression and aspontaneity. He was intolerant of nocturnal continuous positive airway pressure device. Epworth score was 21. Methods Examination demonstrated: marked orthostatic hypotension, preserved cognition, hypersomnolence, dyspraxic dysgraphia, palmar and antecubital agraphaesthesia, downbeat horizontal nystagmus at eccentric gaze positions, square wave jerks, bidirectionally impaired head impulse test, dysmetric saccades, asymmetric cerebellar signs in upper and lower limbs, rightward Pisa syndrome, kinesigenic dystonic axial posturing, rightward laterocollis and equivocal Babinski/Oppenheim reflexes. Gait assessment demonstrated sensory and cerebellar ataxic features with marked apraxia. No pes cavus. Results Computed tomography of brain had Fazekas 1 small vessel disease, Medial temporal atrophy score 1, Koedam 1 and age-commensurate cerebral and cerebellar atrophy. RFC1 gene testing confirmed biallelic intronic AAGGG repeat expansion disorder. Conclusion Cerebellar Ataxia Neuropathy and Vestibular Areflexia Syndrome (CANVAS) should be considered in patients with presentations from mid-life of progressive sensory ataxic neuropathy, altered vestibular ocular reflex, gaze evoked nystagmus and prominent dysautonomia. CANVAS is a rare autosomal recessive genetic disorder with a protean presentation. Referral to Genetics Services should be undertaken for family counselling. Keeping an open mind in complex, multimorbid patients to a potentially unifying diagnosis is important to guide prognostication. The rumble of hooves in the distance is not always that of horses.

Mulberry Twig Alkaloids Improved the Progression of Metabolic-Associated Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating the PGC1α/PPARα and KEAP1/NRF2 Pathways.

Background/Objectives: Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver disorders associated with obesity and metabolic syndrome, and poses a significant global health burden with limited effective treatments. The aim of this study was to assess the protective effects of mulberry twig alkaloids (SZ-A) on MAFLD and to further investigate the underlying mechanisms including the specific targets or pathways. Methods: Diet-induced obesity (DIO) and normal mouse models were established by feeding C57Bl/6J mice with a high-fat diet (HFD) or common diet for 12 weeks. SZ-A, dapagliflozin, and placebo were administered to corresponding mouse groups for 8 weeks. Data of fasting blood glucose, glucose tolerance, insulin tolerance, and the body weight of mice were collected at the baseline and termination of the experiment. Serum liver enzymes and lipids were measured by ELISA. Western blotting, qPCR, and pathological section staining were implemented to evaluate the degrees of liver steatosis, fibrosis, and oxidative stress in mice. Results: In DIO mouse models, high-dose SZ-A (800 mg/kg/d) treatment significantly inhibited HFD-induced weight gain, improved insulin tolerance, and reduced serum alanine aminotransferase, total cholesterol, and triglyceride levels compared with placebo. In DIO mice, SZ-A could alleviate the pathological changes of hepatic steatosis and fibrosis compared with placebo. Lipid catabolism and antioxidant stress-related proteins were significantly increased in the livers of the high-dose SZ-A group (p < 0.05). Inhibition of PGC1α could inhibit the function of SZ-A to enhance lipid metabolism in hepatocytes. PGC1α might interact with NRF2 to exert MAFLD-remedying effects. Conclusions: By regulating the expression of PGC1α and its interacting KEAP1/NRF2 pathway in mouse liver cells, SZ-A played important roles in regulating lipid metabolism, inhibiting oxidative stress, and postponing liver fibrosis in mice with MAFLD.

Interrelationship between Non-Alcoholic Steatohepatitis and Vitamin D: A Mini Review

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by inflammation and accumulation of fat in the liver, often associated with obesity, diabetes and metabolic syndrome leading to fibrosis and ultimately cirrhosis of the liver. The literature search included original articles, randomized controlled trials, cohort studies, case-control studies and review articles from the year 2004 onwards. The electronic databases Cochrane, MEDLINE, ScienceDirect and PubMed were used for the literature search. The current state of evidence shows a positive correlation between non-alcoholic steatohepatitis and vitamin D deficiency. The association between vitamin D and non-alcoholic steatohepatitis (NASH) is a complex one and further studies are needed for understanding this relationship. This review is aimed at the relationship between non-alcoholic steatohepatitis and vitamin D, additionally, it will discuss the role of vitamin D in modulating immune responses with its protective effects on the liver. The need for maintaining an adequate level of vitamin D in at-risk populations will also be discussed along with future research in this matter.

Obesity increases the risk of hepatic fibrosis in young adults with type 2 diabetes mellitus: the need to screen.

The objective of this study was to determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in young compared with older adults. Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated. A total of 243 participants were ages <45 years, and 1177 were ages ≥45 years. Obesity, T2D, and metabolic syndrome were highly prevalent in young adults. Frequencies of steatosis and fibrosis were high in young adults (50.2% and 7.5% vs. older adults 52.7% and 9.9%, respectively) and were significantly higher in those with both obesity and T2D (71.1% and 15.7%, respectively; p < 0.01). In young adults, T2D and obesity were the strongest risk factors for hepatic fibrosis (odds ratios 4.33 [95% CI: 1.37-13.68] and 1.16 [95% CI: 1.07-1.25], respectively; p < 0.05). There is a high prevalence of clinically significant hepatic fibrosis in young adults with cardiometabolic risk factors. Up to one in seven young adults with obesity and T2D had clinically significant hepatic fibrosis on elastography. This highlights the need to screen young adults with cardiometabolic risk factors for MASLD for early detection and intervention.

The Role of Paraclinical Investigations in Detecting Inflammation in Children and Adolescents with Obesity and Metabolic Syndrome.

The aim of our study was to evaluate whether these markers are effective in distinguishing varying degrees of obesity and MetS in children and adolescents. We conducted a retrospective study. A total of 71 children and adolescents, aged between 6 and 16, were included in the study. Among them, 5 were overweight, 35 had obesity, and 31 had severe obesity. According to the NCEP ATP III criteria, 32 individuals had Metabolic Syndrome (MetS), while 39 did not have MetS. The MetS positive group had higher values of TG/HDL-C (p < 0.001), TC/HDL-C (p < 0.001), MHR (p = 0.015), LHR (p = 0.001), NHR (p = 0.001), atherogenic index of plasma (p < 0.001), and PHR (p < 0.001). ESR, NLR, PLR, and SII did not progressively increase with the number of MetS criteria. The ROC curve analysis demonstrated that markers such as TG/HDL-C, the atherogenic index of plasma, TC/HDL-C, LHR, NHR, and PHR were effective in identifying MetS in children and adolescents with obesity. In conclusion, we determined that some novel inflammatory and cardioembolic indexes are useful in assessing MetS and obesity in children and adolescents.

Non-alcoholic fatty liver disease: Genetic susceptibility

The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is increasing, particularly in individuals who consume minimal to no alcohol. Currently, NAFLD affects at least 32% of the global population. Although not all but approximately 5-10% cases of NAFLD progress to non-alcoholic steatohepatitis (NASH), a condition arising from lipotoxicity. Patients with NASH may further develop liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, it is important to note that progression from NAFLD to NASH and HCC is not inevitable for all patients. The pathogenesis of HCC in the context of NAFLD and NASH remains poorly understood, however, fat accumulation, often due to obesity or metabolic syndrome, leads to lipotoxicity. In individuals with type 2 diabetes (T2D), elevated insulin levels promote lipolysis in adipose tissue and activate lipid-synthesizing enzymes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), which contribute to lipid accumulation in the liver. Additionally, high glucose levels in T2D can alter gene regulation by activating carbohydrate response-element binding protein (ChREBP) and insulin can increase the activity of sterol regulatory element binding protein (SREBP-1c). These lipogenic transcription factors are known to directly or indirectly activate patatin-like phospholipase domain-containing protein 3 (PNPLA3). Recent research has found elevated levels of angiotensinogen (AGT) and des-angiotensin in both experimental animals and patients with NAFLD. Emerging evidence highlights the significance of genetic factors in the risk of developing NAFLD. Here we explore the association between specific genes and hepatosteatosis, detailing the roles of T2D and obesity in the progression from NAFLD to NASH, and involvement of hepatic stellate cells in liver fibrosis. Additionally, we examine the impact of genes such as PNPLA3, MBOAT7, TM6SF2, GKRP, CCN3, and AGT as well as role of single nucleotide polymorphisms in gene regulation and their contribution to the risk of NAFLD.

TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH.

For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.

Effect of deep brain stimulation on postoperative body mass index: A systematic review and meta-analysis.

Deep Brain Stimulation (DBS) is FDA-approved for several movement disorders; such as Parkinson's disease, dystonia, and neuropsychiatric disorders. There are various reports of Body mass index (BMI) changes following different DBS targets in various disorders. A comprehensive systematic review and meta-analysis were conducted to investigate the impact of DBS on patients' Body Mass Index (BMI) and provide an in-depth overview of its underlying mechanisms. We conducted research according to PRISMA guidelines. Our study assessed comprehensively electronic databases, including Pubmed, Scopus, Embase, web of science, and the Cochrane Library, up to May 2024. The random-effect model analysis was performed by the Comprehensive Meta-analysis software (CMA) version 3.0. As well, Cochran's Q test was used to determine the statistical heterogeneity of included studies. This systematic review ultimately included 49 studies, 46 of which entered the meta-analysis. The total number of patients was 1478, consisting of Parkinson's disease (PD), dystonia, and the obsessive compulsive disorder (OCD) patients. The most common DBS target was subthalamic nucleus, followed by globus pallidus internus (GPi). Our meta-analysis depicted the BMI of participants significantly mount after DBS electrode implantation (SMD = -0.542, 95%CI: -0.678 to -0.406, and P-value < 0.001). However, moderate to high heterogeneity was detected among the studies (I2 = 67.566%). Additionally, the Daily energy intake (DEI) of patients significantly decreased after DBS (SMD: 0.457, 95%CI; 0.205 to 0.709, and P-value < 0.001). STN and GPi DBS can lead to weight gain through distinct central pathways in various movement and neuropsychiatric disorders, posing a potential risk for obesity, insulin resistance, and metabolic syndrome.