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Medicine May 2024The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes.
METHODS
For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023.
RESULTS
Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)].
CONCLUSIONS
In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results.
Topics: Humans; Orlistat; Prediabetic State; Diabetes Mellitus, Type 2; Blood Glucose; Disease Progression; Anti-Obesity Agents; Randomized Controlled Trials as Topic; Lactones
PubMed: 38787971
DOI: 10.1097/MD.0000000000038354 -
Food Research International (Ottawa,... Jul 2024The scourge of obesity arising from obesogens and poor dieting still ravages our planet as half of the global population may be overweight and obese by 2035. This... (Review)
Review
The scourge of obesity arising from obesogens and poor dieting still ravages our planet as half of the global population may be overweight and obese by 2035. This metabolic disorder is intertwined with type 2 diabetes (T2D), both of which warrant alternative therapeutic options other than clinically approved drugs like orlistat with their tendency of abuse and side effects. In this review, we comprehensively describe the global obesity problem and its connection to T2D. Obesity, overconsumption of fats, the mechanism of fat digestion, obesogenic gut microbiota, inhibition of fat digestion, and natural anti-obesity compounds are discussed. Similar discussions are made for diabetes with regard to glucose regulation, the diabetic gut microbiota, and insulinotropic compounds. The sources and production of anti-obesity bioactive peptides (AOBPs) and anti-diabetic bioactive peptides (ADBPs) are also described while explaining their structure-function relationships, gastrointestinal behaviors, and action mechanisms. Finally, the techno-functional applications of AOBPs and ADBPs are highlighted.
Topics: Humans; Obesity; Peptides; Anti-Obesity Agents; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Animals
PubMed: 38763677
DOI: 10.1016/j.foodres.2024.114427 -
Biomaterials Sep 2024The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the...
The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.
Topics: Cholangiocarcinoma; Animals; Mitochondria; Drug Delivery Systems; Humans; Drug Resistance, Neoplasm; Lipid Metabolism; Cell Line, Tumor; Mice; Bile Duct Neoplasms; CD36 Antigens; Metal-Organic Frameworks; Antineoplastic Agents; Mice, Nude; Reactive Oxygen Species; Mice, Inbred BALB C; Lipase
PubMed: 38754290
DOI: 10.1016/j.biomaterials.2024.122609 -
European Journal of Heart Failure May 2024Approximately 30-49% of heart failure (HF) patients are living with obesity. The recommended body mass index (BMI) for the general population is 18.5-24.9 kg/m. The... (Review)
Review
Approximately 30-49% of heart failure (HF) patients are living with obesity. The recommended body mass index (BMI) for the general population is 18.5-24.9 kg/m. The obesity paradox suggests that HF patients with obesity (HFpwO) have a better prognosis compared to normal BMI. Guideline recommendations on ideal BMI for HFpwO are limited. This systematic review aims to examine the evidence base for intentional weight loss in HFpwO on the following parameters: mortality, hospitalization, symptoms, quality of life (QOL), effects on left ventricular ejection fraction (LVEF) and adverse events. A total of 22 studies were identified: lifestyle intervention (n = 9), pharmacotherapy (n = 3), bariatric surgery (n = 10). Mortality and hospitalization, symptoms, QOL, and LVEF were reported in 8, 15 and 14 studies, respectively. All studies had moderate to high risk of bias except one randomized controlled trial (RCT) which evaluated semaglutide in HF with preserved ejection fraction (HFpEF) patients. Semaglutide resulted in weight loss with improvement in QOL. Lifestyle intervention led to weight loss, minimal adverse events, and improvement in symptoms in both HF with reduced ejection fraction (HFrEF) and HFpEF patients. In six observational studies, bariatric surgery in HFrEF patients achieved weight loss and improvement in LVEF safely in most patients but some patients developed worsening HF perioperatively. There is a need for high-quality adequately powered RCTs on intentional weight loss in HFpwO with survival and hospitalization outcomes. All forms of weight loss intervention studied in this review were likely to result in significant weight loss, improved symptoms and QOL. Careful monitoring is required due to an increase in certain adverse events.
PubMed: 38752254
DOI: 10.1002/ejhf.3270 -
The Lancet. Diabetes & Endocrinology Jun 2024Medications for obesity have been studied in various populations over the past three decades. We aimed to quantify the baseline demographic characteristics of BMI, sex,... (Review)
Review
Medications for obesity have been studied in various populations over the past three decades. We aimed to quantify the baseline demographic characteristics of BMI, sex, age, and race in randomised clinical trials (RCTs) across three decades to establish whether the population studied is representative of the global population affected by the disease. Clinical trials of 12 medications for obesity (ie, orlistat, naltrexone-bupropion, topiramate-phentermine, liraglutide, semaglutide, lorcaserin, sibutramine, rimonabant, taranabant, tirzepatide, retatrutide, and orforglipron) published from Jan 20, 1999, to Nov 12, 2023, were assessed through a systematic review for methodological quality and baseline demographic characteristics. 246 RCTs were included, involving 139 566 participants with or without type 2 diabetes. Most trials over-recruited White, female participants aged 40 years or older with class 1 (30·0-34·9 kg/m) and class 2 (35·0-39·9 kg/m) obesity; older participants, those with class 3 (≥40·0 kg/m) obesity, non-White participants, and male participants were under-recruited. Our systematic review suggests that future trials need to recruit traditionally under-represented populations to allow for accurate measures of efficacy of medications for obesity, enabling more informed decisions by clinicians. It is also hoped that these data will help to refine trial recruitment strategies to ensure that future studies are relevant to the population affected by obesity.
Topics: Humans; Obesity; Anti-Obesity Agents; Female; Male; Body Mass Index; Sex Factors; Randomized Controlled Trials as Topic; Racial Groups; Adult
PubMed: 38723646
DOI: 10.1016/S2213-8587(24)00098-6 -
Expert Review of Endocrinology &... May 2024Obesity is the modern world's current epidemic, with substantial health and economic impact. This study aimed to provide a narrative overview of the past, currently... (Review)
Review
INTRODUCTION
Obesity is the modern world's current epidemic, with substantial health and economic impact. This study aimed to provide a narrative overview of the past, currently available, and future treatment options that offer therapeutic and preventive advantages for obesity management.
AREAS COVERED
Historically, rimonabant, and lorcaserin, were approved and used for managing non-syndromic obesity. Currently, orlistat, naltrexone/bupropion, glucagon-like peptide-1 receptor agonist (GLP-1 RA), and a few promising therapeutic agents are under investigation, including retatrutide, cagrilintide and orforglipron, which show promising weight reduction effects. We have developed a search string of the Medical Subject Headings (MeSH), including the terms GLP-1 RAs, obesity, and weight loss. This string was then used to perform a systematic literature search in the database including PubMed, EMBASE, MEDLINE, and Scopus up to January 31, 2024.
EXPERT OPINION
Managing obesity often requires medical interventions, particularly in cases of severe obesity or obesity-related comorbidities. Thus, it is important to approach obesity management holistically, considering individual needs and circumstances. In our opinion, consulting with healthcare professionals is crucial to developing a personalized plan that addresses both weight loss and overall health improvement.
Topics: Humans; Obesity; Anti-Obesity Agents; Weight Loss; Obesity Management
PubMed: 38685693
DOI: 10.1080/17446651.2024.2347258 -
Cancers Apr 2024This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with...
Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings-A Pilot Study.
BACKGROUND
This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry.
METHODS
Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed.
RESULTS
At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group ( < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group ( < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively.
CONCLUSIONS
Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis.
PubMed: 38672673
DOI: 10.3390/cancers16081591 -
BMC Complementary Medicine and Therapies Apr 2024Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms....
BACKGROUND
Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A. baumannii infections are urgently needed. In recent years, Brassica vegetables have received a lot of attention since their phytochemical compounds have been directly linked to diverse antimicrobial actions by inhibiting the growth of various Gram-positive and Gram-negative bacteria, yeast, and fungi. Despite their longstanding antibacterial history, there is currently a lack of scientific evidence to support their role in the management of infections caused by the nosocomial bacterium, A. baumannii. This study aimed to address this gap in knowledge by examining the antibacterial and lipase inhibitory effects of six commonly consumed Brassica greens, Chinese cabbage (CC), curly and Tuscan kale (CK and TK), red and green Pak choi (RP and GP), and Brussels sprouts (BR), against A. baumannii in relation to their chemical profiles.
METHODS
The secondary metabolites of the six extracts were identified using LC-QTOF-MS/MS analysis, and they were subsequently correlated with the lipase inhibitory activity using multivariate data analysis and molecular docking.
RESULTS
In total, 99 metabolites from various chemical classes were identified in the extracts. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed the chemical similarities and variabilities among the specimens, with glucosinolates and phenolic compounds being the major metabolites. RP and GP showed the highest antibacterial activity against A. baumannii, followed by CK. Additionally, four species showed a significant effect on the bacterial growth curves and demonstrated relevant inhibition of A. baumannii lipolytic activity. CK showed the greatest inhibition (26%), followed by RP (21%), GP (21%), and TK (15%). Orthogonal partial least squares-discriminant analysis (OPLS-DA) pinpointed 9 metabolites positively correlated with the observed bioactivities. Further, the biomarkers displayed good binding affinities towards lipase active sites ranging from -70.61 to -30.91 kcal/mol, compared to orlistat.
CONCLUSION
This study emphasizes the significance of Brassica vegetables as a novel natural source of potential inhibitors of lipase from A. baumannii.
Topics: Brassica; Acinetobacter baumannii; Molecular Docking Simulation; Anti-Bacterial Agents; Tandem Mass Spectrometry; Gram-Negative Bacteria; Gram-Positive Bacteria; Phytochemicals; Lipase
PubMed: 38641582
DOI: 10.1186/s12906-024-04460-y -
Open Veterinary Journal Jan 2024Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is...
The corrective role of superparamagnetic iron oxide nanoparticles for the genes controlling hypothalamus-pituitary-testis-axis in male obesity-associated secondary hypogonadism.
BACKGROUND
Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields.
AIM
In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat).
METHODS
42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments.
RESULTS
The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility.
CONCLUSION
CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.
Topics: Rats; Male; Animals; Leptin; Orlistat; Testis; Obesity; Hypogonadism; Hypothalamus; Gonadotropin-Releasing Hormone; Magnetic Iron Oxide Nanoparticles; Rodent Diseases
PubMed: 38633156
DOI: 10.5455/OVJ.2024.v14.i1.39 -
Journal of Endocrinological... Jun 2024This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic...
AIM
This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification.
METHODS
Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote.
RESULTS
The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m and < 40 kg/m associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative.
CONCLUSION
The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
Topics: Humans; Obesity; Overweight; Adult; Italy; Comorbidity; Behavior Therapy; Practice Guidelines as Topic; Disease Management; Bariatric Surgery
PubMed: 38630213
DOI: 10.1007/s40618-024-02361-y