A5102954823- Diet and metabolism studies
- Pancreatic function and diabetes
- Cannabis and Cannabinoid Research
- Bariatric Surgery and Outcomes
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Diabetes Treatment and Management
- Glycogen Storage Diseases and Myoclonus
- Epigenetics and DNA Methylation
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Birth, Development, and Health
- Adenosine and Purinergic Signaling
- Adipose Tissue and Metabolism
- Angiogenesis and VEGF in Cancer
- Fibroblast Growth Factor Research
- Gastroesophageal reflux and treatments
- Biomedical Research and Pathophysiology
- Biochemical effects in animals
- Biomarkers in Disease Mechanisms
- MicroRNA in disease regulation
- Dietary Effects on Health
Hebrew University of Jerusalem
2018-2025
Aging is an established risk factor for vascular diseases, but aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that endothelial growth (VEGF) signaling insufficiency, which caused by increased production decoy receptors, drive physiological across multiple systems. Increasing VEGF prevented age-associated capillary loss, improved perfusion and function, extended life span. Healthier was evidenced favorable metabolism body composition...
Significance Statement This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in pathogenesis obesity-induced CKD. Our data demonstrate that ANT2 depletion renal proximal tubule cells (RPTCs) leads to a shift their primary metabolic program from fatty acid oxidation aerobic glycolysis, resulting mitochondrial protection, cellular survival, and preservation function. These findings provide new insights into underlying mechanisms CKD have potential be translated...
Export Altered glucose reabsorption via the facilitative transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating cannabinoid-1 receptor (CB1R), which contributes development of diabetic nephropathy (DN). However, link between CB1R GLUT2 remains be determined. Here, we show that chronic peripheral blockade or genetically inactivating CB1Rs in RPTCs ameliorated...
Article6 September 2021Open Access Source DataTransparent process Alleviation of a polyglucosan storage disorder by enhancement autophagic glycogen catabolism Or Kakhlon Corresponding Author [email protected] orcid.org/0000-0001-7435-6454 Department Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Search for more papers this author Hilla Vaknin orcid.org/0000-0001-9101-1423 Laboratory Neurodegenerative Diseases and Personalized Medicine, The Cell Screening Facility...
To evaluate the specific role of endocannabinoid/cannabinoid type-1 (CB1 R) system in modulating mitochondrial dynamics metabolically active renal proximal tubular cells (RPTCs).We utilized mitochondrially-targeted GFP live (wild-type and null for CB1 electron microscopy kidney sections RPTC-CB1 R-/- mice their littermate controls. In both vitro vivo conditions, we assessed ability R agonism or fatty acid flux to modulate architecture function.Direct stimulation resulted fragmentation RPTCs....
T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how cells adapt to this metabolic challenge, we generate cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss Ant2, crucial protein mediating exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding regeneration. Interestingly, Ant2-/- naïve exhibit enhanced...
Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction glucose production. It not clear whether these outcomes are entirely due to or the new anatomy imposed by surgery contributes metabolic function of liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided high-fat high-sucrose diet compared them weight-matched sham-operated (WMS). At 40 days after surgery, VSG-operated displayed less WMS. By measuring...
The endocannabinoid system (ECS) regulates various physiological processes, including energy homeostasis and kidney function. ECS upregulation in obese animals humans suggests a potential link to obesity-induced chronic disease (CKD). However, changes the are mainly studied rodents, leaving impact on unknown. In this study, total of 21 lean males (38–71 years) underwent biopsy. Biochemical analysis, histology, (eCB) assessment were performed tissue blood samples. Correlations between...
Obesity is a global medical problem; its common form known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such Prader-Willi syndrome (PWS), that also associated with (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO and GIO very limited, they result in only partial improvement. Cannabidiolic acid (CBDA), constituent of Cannabis sativa, gradually decarboxylates to cannabidiol (CBD). Whereas the anti-obesity properties CBD...
Over-activation of the endocannabinoid/CB1R system is a hallmark feature obesity and its related comorbidities, most notably type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD). Although use drugs that widely block CB1R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered valid therapeutic option due their adverse neuropsychiatric side effects. Here, we describe novel nanotechnology-based drug delivery...
Both diabetes and obesity (diabesity) contribute significantly to the development of chronic kidney disease (CKD). In search new remedies reverse or arrest progression CKD, we examined therapeutic potential a novel compound, AN1284, in mouse models CKD induced by type-2 with obesity. Six week-old BKS Cg-Dock 7m+/+ Leprdb/J mice type 2 were treated AN1284 (2.5 5 mg.kg-1 per day) via micro-osmotic pumps implanted subcutaneously for 3 months. Measures included renal, pancreatic, liver...
Abstract T-cell activation requires a substantial increase in NAD + production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generated cell-specific ADP/ATP translocase-2 knockout (Ant2 −/− ) mice. Loss Ant2, crucial protein mediating exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, impeding regeneration. Interestingly, Ant2 naïve exhibited...
A mouse model for one anastomosis gastric bypass (OAGB) surgery displays similar outcomes to clinical reports and enables study the weight loss-dependent -independent effects of this bariatric surgery.
Bariatric surgeries induce weight loss which is associated with an improvement in hepatic steatosis and reduction glucose production. It not clear whether these outcomes are entirely due to weight-loss, or the new anatomy imposed by surgery contributes metabolic function of liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided a high-fat high-sucrose diet, compared them diet weight-matched sham-operated (WMS). 40 days after surgery, VSG-operated displayed lesser WMS....
Abstract Bariatric surgery is an effective obesity treatment, leading to weight loss and improvement in glycemia, that characterized by hypersecretion of gastrointestinal hormones. However, regain relapse hyperglycemia are not uncommon. Here, we investigated the role somatostatin (Sst) bariatric outcomes using a mouse model sleeve gastrectomy (SG). Sst knockout (sst-ko) mice fed with calorie-rich diet gained normally, had mild favorable metabolic phenotype compared heterozygous sibling...
Abstract BACKGROUND AND AIMS Obesity, a widespread condition with an ever-increasing prevalence, imposes great medical concern since it serves as risk factor for wide range of conditions, including the development chronic kidney disease (CKD). Lipid accumulation and impaired fatty acid β-oxidation in renal proximal tubular cells (RPTCs) well overall mitochondrial dysfunction have been shown to induce injury, inflammation fibrosis, leading CKD. However, molecular mechanisms linking RPTCs...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Abstract This work employs Adult Polyglucosan Body Disease (APBD) models to explore the efficacy and mechanism of action 144DG11, a new polyglucosan-reducing lead compound discovered by high-throughput screen (HTS). APBD is an adult onset glycogen storage disorder (GSD) manifesting as debilitating progressive axonopathic leukodystrophy. caused branching enzyme (GBE) deficiency leading poorly branched insoluble inclusions, which precipitate neuropathogenic polyglucosans (PG). 144DG11 led...
Bariatric surgeries induce weight loss which is associated with an improvement in hepatic steatosis and reduction glucose production. It not clear whether these outcomes are entirely due to weight-loss, or the new anatomy imposed by surgery contributes metabolic function of liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided a high-fat high-sucrose diet, compared them diet weight-matched sham-operated (WMS). 40 days after surgery, VSG-operated displayed lesser WMS....