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Proceedings (Baylor University. Medical... 2024Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease worldwide. Orlistat blocks intestinal fat absorption, leading to decreased liver fat content. Therefore, it is a viable option for NAFLD management. We performed a systematic review and metaanalysis using randomized controlled trials (RCTs). We used mean difference (MD) to pool continuous outcomes presented with the corresponding confidence interval (CI). We included four RCTs with a total of 379 patients. Orlistat was effective in reducing liver fat content (MD: -5.02, 95% CI [-7.23, -2.82], = 0.00001), alanine transferase (MD: -10.03, 95% CI [-17.80, -2.26], = 0.01), aspartate transferase (MD: -4.29, 95% CI [-7.59, -0.99], = 0.01), waist circumference (MD: -3.18, 95% CI [-4.25, -2.10], = 0.00001), body mass index (MD: -1.03, 95% CI [-1.34, -0.73], = 0.00001), total cholesterol (MD: -3.75, 95% CI [-4.02, -3.49], = 0.00001), and low-density lipoprotein (MD: -3.83, 95% CI [-4.05, -3.61], = 0.00001). However, orlistat was associated with increased serum triglycerides (MD: 7.46, 95% CI [6.48, 8.44], = 0. 00001). Orlistat is a viable option for NAFLD management; however, it increases triglyceride levels. Larger RCTs are required.
PubMed: 38910819
DOI: 10.1080/08998280.2024.2335829 -
Annales D'endocrinologie Jun 2024During the past years, several drugs have been developed for the treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists... (Review)
Review
During the past years, several drugs have been developed for the treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists (RA), GLP-1/GIP biagonists and the melanocortin 4 receptor (MC4R) agonist, setmelanotide. Some should be available in the future: GLP-1/glucagon biagonists, GLP-1/GIP/glucagon triagonists. These drugs act mainly by reducing food intake or fat absorption. However, many of them show specific effects on the adipose tissue. All these drugs show significant reduction of fat mass and, more particularly of visceral fat. If most of the drugs, except orlistat, have been shown to increase energy expenditure in rodents with enhanced thermogenesis, this has not yet been clearly demonstrated in humans. However, biagonists or triagonist stimulating glucagon seem to a have a more potent effect to increase thermogenesis in the adipose tissue and, thus, energy expenditure. Most of these drugs have been shown to increase the production of adiponectin and to reduce the production of pro-inflammatory cytokines by the adipose tissue. GLP-1RAs reduce the size of adipocytes and promote their differentiation. GLP-1RAS and GLP-1/GIP biagonists reduce, in the adipose tissue, the expression of several genes involved in lipogenesis. Further studies are still needed to clarify the precise roles, on the adipose tissue, of these drugs dedicated for the treatment of obesity.
Topics: Humans; Obesity; Anti-Obesity Agents; Adipose Tissue; Animals; Energy Metabolism; Glucagon-Like Peptide-1 Receptor; Thermogenesis; Glucagon-Like Peptide 1; Orlistat
PubMed: 38871515
DOI: 10.1016/j.ando.2024.05.021 -
Acta Pharmaceutica Sinica. B Jun 2024Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic...
Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, , Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.
PubMed: 38828148
DOI: 10.1016/j.apsb.2024.03.024 -
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 -
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 -
European Journal of Pharmaceutical... Jun 2024Lipid-based formulations (LBFs) are an enabling-formulation approach for lipophilic poorly water-soluble compounds. In LBFs, drugs are commonly pre-dissolved in lipids,...
Lipid-based formulations (LBFs) are an enabling-formulation approach for lipophilic poorly water-soluble compounds. In LBFs, drugs are commonly pre-dissolved in lipids, and/or surfactants/cosolvents, hereby avoiding the rate-limiting dissolution step. According to the Lipid formulation classification system, proposed by Pouton in 2006, in type II LBFs a surfactant with an HLB-value lower than 12 is added to the lipids. If high drug doses are required, e.g. for preclinical toxicity studies, supersaturated LBFs prepared at elevated temperatures may be a possibility to increase drug exposure. In the present study, the impact of digestion on drug absorption in rats was studied by pre-dosing of the lipase inhibitor orlistat. The lipid chain length of the type II LBFs was varied by administration of a medium-chain- (MC) and a long-chain (LC)-based formulation. Different drug doses, both non-supersaturated and supersaturated, were applied. Due to an inherent precipitation tendency of cinnarizine in supersaturated LBFs, the effect of the addition of the precipitation inhibitor Soluplus® was also investigated. The pharmacokinetic results were also evaluated by multiple linear regression. In most cases LC-based LBFs did not perform better in vivo, in terms of a higher area under the curve (AUC) and maximal plasma concentration (C), than MC-based LBFs. The administration of supersaturated LBFs resulted in increased AUC (1.5 - 3.2-fold) and C (1.1 - 2.6-fold)-values when compared to the non-supersaturated equivalents. Lipase inhibition led to a decreased drug exposure in most cases, especially for LC formulations (AUC reduced to 47 - 67%, C to 46 - 62%). The addition of Soluplus® showed a benefit to drug absorption from supersaturated type II LBFs (1.2 - 1.7-fold AUC), due to an increased solubility of cinnarizine in the formulation. Upon dose-normalization of the pharmacokinetic parameters, no beneficial effect of Soluplus® could be demonstrated.
Topics: Cinnarizine; Animals; Male; Lipids; Solubility; Lactones; Rats, Wistar; Orlistat; Intestinal Absorption; Rats; Polyethylene Glycols; Lipase; Polyvinyls; Chemical Precipitation; Surface-Active Agents; Chemistry, Pharmaceutical
PubMed: 38608735
DOI: 10.1016/j.ejps.2024.106765 -
Biomedicines Mar 2024The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity,... (Review)
Review
BACKGROUND
The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s.
METHODS
The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers' databases, complemented by a cross-check of the reference lists. We used a combination of the search terms "polycystic ovary syndrome", "obesity" and "insulin resistance" with "metformin", "exenatide", "liraglutide", "semaglutide", "orlistat" and terms relevant to the topic of each paragraph (e.g., "pathophysiology", "metabolism", "infertility", "treatment").
RESULTS
All articles describing the mechanisms responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s, were considered for this review.
CONCLUSIONS
The existing research on GLP-1 receptor agonists (GLP-1RAs) has not conclusively established a specific therapeutic use for these drugs. Additionally, the efficacy of the newer generation of GLP-1RAs, particularly in terms of dosage and duration of exposure, warrants more extensive research. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.
PubMed: 38540265
DOI: 10.3390/biomedicines12030653