Publications by authors named "William S Blaner"
Article Synopsis
- Dysregulation of retinoid metabolism is linked to serious eye diseases, and enhancing this metabolism through drugs shows potential for treatment.
- CRBP1, the main transporter of retinol in the eye, is inhibited to protect retinas from damage, and researchers have identified new nonretinoid inhibitors through high-throughput screening.
- By analyzing CRBP1's structure and its interactions with these inhibitors, the study paves the way for designing better treatments targeting this lipid-binding protein.
Article Synopsis
- Retinol-binding protein 2 (RBP2) is crucial for vitamin A transport in gut cells, and mice without it show obesity and glucose issues.
- This study investigated how different vitamin A diets impact the function and gene expression of incretin-secreting cells in RBP2-deficient mice compared to controls.
- Results indicated that RBP2 mice gained more weight and had elevated GIP levels on a normal vitamin A diet, while their GIP response decreased on a low vitamin A diet, highlighting RBP2's role in incretin regulation and gene expression related to enter endocrine cells.
Article Synopsis
- Vitamin A is a crucial micronutrient for vertebrates, but how the body maintains its balance is not well understood.
- This study examined the role of the hypothalamus in regulating vitamin A levels in the liver and bloodstream by injecting retinoids into the brains of rats and altering retinoid levels in mice.
- Findings suggest that the brain can detect changes in vitamin A and may play a significant role in controlling its overall balance in the body.
Article Synopsis
- Transthyretin amyloid cardiomyopathy (ATTR-CM) is a significant cause of heart failure in older adults, often linked to a specific genetic variant (pV142I) primarily found in individuals of West African descent.
- The SCAN-MP study aims to determine how prevalent ATTR-CM is in older Black and Caribbean Hispanic patients with heart failure, using noninvasive imaging techniques.
- This study is the largest of its kind focusing on cardiac amyloidosis in these populations and could lead to better treatment strategies using the approved drug tafamidis.
Article Synopsis
- Perturbed mitochondrial function and Vitamin A metabolism are linked to diet-induced obesity and type 2 diabetes.
- A murine model was used to explore how Vitamin A impacts mitochondrial activity and organ changes in response to a high-fat diet.
- The findings show that Vitamin A influences organ remodeling and steatosis without affecting mitochondrial function in the liver, muscle, or kidney during high-fat feeding.
Article Synopsis
- Retinoids are crucial for regulating cell processes like proliferation and differentiation, particularly in the lung alveolus during inflammation.
- Research in male mice highlights the importance of local retinoid stores in lung health during an acute inflammatory response, specifically when exposed to lipopolysaccharide.
- The study reveals that not just lipofibroblasts, but also microvascular endothelial and alveolar epithelial cells, can accumulate retinoids and play significant roles in responding to inflammation.
Article Synopsis
- Efficient vitamin A delivery to the retinal pigment epithelium is crucial for producing 11-cis-retinal, essential for vision; RBP4 is the main carrier in the plasma.
- In Rbp4-deficient mice, levels of 11-cis-retinaldehyde and all-trans-retinyl ester were significantly reduced, leading to noticeable photoreceptor cell loss by 8 months.
- Despite the deficiency of RBP4, the study indicates that alternative pathways may exist for delivering vitamin A to the retina, as some visual cycle products were still measurable.
Vitamin A preserves cardiac energetic gene expression in a murine model of diet-induced obesity.
Am J Physiol Heart Circ Physiol
December 2022
Article Synopsis
- * Researchers tested whether a lack of vitamin A accelerates cardiomyopathy in mice with diet-induced obesity by subjecting them to a high-fat diet devoid of vitamin A, while control mice received a nutrient-sufficient diet.
- * Findings revealed that while cardiac function and mitochondrial respiration were largely maintained despite vitamin A deficiency, the expression of key genes related to cardiac energy metabolism was significantly dependent on vitamin A, indicating its crucial role in preserving cardiac health in obesity.
Article Synopsis
- The study investigates the integration of genetic information with metabolomics to understand how genes influence metabolism, focusing specifically on a diverse population rather than just individuals of European ancestry.* -
- Researchers conducted a whole genome association study involving 2,466 Black individuals, identifying 519 associations between genetic loci and metabolite peaks, many linked to ancestry-specific alleles.* -
- By using advanced techniques like tandem mass spectrometry, the study also aims to provide insights into unknown metabolites and hereditary diseases related to the findings, such as transthyretin amyloidosis and sickle cell disease.*
Article Synopsis
- Lumbar spinal stenosis (LSS) surgery often involves the resection of ligamentum flavum, and this study examined the potential presence of transthyretin (TTR) amyloid in older patients, which could be a modifiable factor in LSS cases.
- In a study of 47 older adults undergoing lumbar spine decompression, amyloid was found in 34% of participants, with a higher prevalence in those aged 75 and older.
- The study identified TTR as the precursor protein in a majority of amyloid cases, but clinical and quality-of-life measures did not show significant differences between patients with or without amyloid.
Article Synopsis
- Rbp2-/- mice are more susceptible to obesity and related metabolic issues compared to control mice, showing dysregulated levels of the hormone GIP.
- Research indicates that RBP2 is largely present in enteroendocrine cells (EECs) responsible for producing hormones like GIP and glucagon-like peptide-1, and these cells also have the machinery to synthesize retinoic acid.
- The study finds that Rbp2-/- mice have fewer total and GIP-positive EECs, suggesting that RBP2 and retinoic acid play important roles in the development and functioning of these hormone-producing cells.
Retinol-binding protein 2 (RBP2): More than just dietary retinoid uptake.
Biochim Biophys Acta Mol Cell Biol Lipids
August 2022
Article Synopsis
- RBP2 (Retinol-binding protein 2) is essential for absorbing and metabolizing dietary vitamin A in the small intestine, primarily found in its proximal section at a concentration of 0.1-0.5% of soluble protein.
- Recent studies show that RBP2 has a high affinity for binding monoacylglycerols, including the endocannabinoid 2-arachidonoylglycerol (2-AG), indicating its role in lipid metabolism.
- Mice lacking RBP2 are more prone to obesity and metabolic issues on a high-fat diet, releasing more of the hormone GIP after an oral fat challenge, highlighting its importance in regulating fat intake and metabolism.
Article Synopsis
- * Alcohol depletes vitamin A in the liver, and this study investigates whether this depletion is primarily due to the action of specific enzymes called Cytochrome P450 (CYPs), particularly CYP2E1.
- * Results show that chronic alcohol intake leads to a significant decrease in vitamin A levels in the liver and is correlated with the increased expression of multiple retinoid-catabolizing CYPs, including CYP26A1 and CYP26B1, in mice.
Article Synopsis
- Vitamin A, through its active form all--retinoic acid, influences the expression of many genes but is often mistakenly labeled as an antioxidant like vitamins C and E.
- The review highlights the confusion surrounding vitamin A's role in the body and also examines the claims about vitamin E being a transcriptional regulator.
- The authors conclude that vitamin A acts mainly as an indirect antioxidant by regulating genes related to antioxidant responses, while vitamin E is a direct antioxidant but lacks strong evidence for direct transcriptional regulation.
Article Synopsis
- CRBP2 is a protein in the small intestine that helps with the uptake and metabolism of dietary retinoids, but recent findings indicate it also interacts with lipid molecules, suggesting a role in lipid metabolism and signaling.
- Researchers conducted a high-throughput screening to identify CRBP2's interactions with various bioactive lipids, discovering its selective affinity for certain monoacylglycerols (MAGs) that are rich in polyunsaturated fatty acids.
- The study also detailed specific amino acids in CRBP2 that enhance its ability to bind with MAGs, providing insights into how this protein may regulate lipid homeostasis differently than the more retinoid-specific CRBP1.
Article Synopsis
- Retinol-binding protein 2 (RBP2) is crucial for absorbing and metabolizing dietary retinoids in the small intestine, and its absence can lead to severe health issues, especially under dietary stress or high-fat conditions.
- Studies show that RBP2 is not only important for retinoid transport but also binds long-chain monoacylglycerols (2-MAGs), including endocannabinoids, indicating a dual role in metabolism.
- The lack of RBP2 leads to significant metabolic problems in mice, such as obesity and insulin intolerance, and raises questions about how its binding functions affect health and hormone levels.
Article Synopsis
- Retinol-binding protein 2 (RBP2) is important for absorbing dietary retinoids in the small intestine, and its absence in mice leads to increased body weight, impaired glucose metabolism, and higher liver triglycerides as they age.
- These issues are also seen in young mice on a high-fat diet, indicating a broader metabolic impact.
- RBP2 acts as a binding protein for monoacylglycerols (MAGs), engaging with the endocannabinoid 2-AG, which suggests that RBP2 plays a crucial role in regulating energy balance and signaling beyond its function in retinoid absorption.
Article Synopsis
- * Researchers found that targeting MERTK, a gene linked to liver fibrosis in humans, can decrease liver fibrosis in mice with NASH, which aligns with human genetic observations.
- * The study suggests that the MerTK receptor in liver macrophages activates specific pathways that lead to HSC activation and liver fibrosis, highlighting the importance of liver macrophages in the progression of NASH.
Constitutive androstane receptor mediates PCB-induced disruption of retinoid homeostasis.
Toxicol Appl Pharmacol
October 2019
Article Synopsis
- Environmental exposure to PCBs, specifically PCB153, disrupts retinoid (vitamin A) homeostasis, which may increase metabolic disease risk.
- The study identifies the constitutive androstane receptor (CAR) as a key mediator in this disruption, particularly through the activation of liver enzymes that affect retinoid metabolism.
- Dietary retinoids can reverse the changes caused by PCB153, suggesting that CAR activation and subsequent retinoid imbalance could play a significant role in the obesogenic effects of PCBs.
Article Synopsis
- All-trans-retinoic acid (ATRA) is known to aid early fat cell differentiation and metabolism, but its effects in mature fat cells have been unclear.
- Researchers disrupted RAR signaling in mature adipocytes by using a dominant negative RARα mutant, resulting in lower ATRA levels in fat and liver tissues.
- This disruption led to poorer glucose clearance, increased liver fat, and reduced thermogenesis, indicating a potential link to metabolic diseases like hepatic steatosis in mice on a regular diet.
Article Synopsis
- Retinol-binding protein 4 (RBP4) is a blood transporter for vitamin A and is linked to various health issues like diabetes and obesity.
- New research shows that increasing RBP4 in fat cells can lead to liver fat accumulation in mice.
- The study introduces new RBP4 antagonists that significantly lower RBP4 levels and show promise for treating nonalcoholic fatty liver disease (NAFLD) in specific mouse models.
Hepatic stellate cell activation: A source for bioactive lipids.
Biochim Biophys Acta Mol Cell Biol Lipids
May 2019
Article Synopsis
- * Activated HSCs accumulate specific polyunsaturated fatty acids like arachidonic and docosahexaenoic acids, along with increased expression of fatty acid metabolism-related genes.
- * The research found an increase in bioactive lipid mediators, including endocannabinoids and ceramides, suggesting that lipid redistribution in activated HSCs influences liver signaling processes.
Article Synopsis
- - Cellular retinol-binding proteins (CRBPs) are crucial for transporting and managing vitamin A in the body, making them potential targets for treating various health issues.
- - Abnormal cannabidiol (abn-CBD) has been identified as a specific inhibitor of CRBP1, with studies showing how it binds effectively to the protein and alters retinoid flow in living organisms.
- - Research demonstrates that abn-CBD can protect eyes from light damage in mice, suggesting it could lead to new treatments for diseases linked to retinoid metabolism imbalances.
Article Synopsis
- Recent literature suggests that vitamin A plays a significant role in preventing and causing metabolic diseases, particularly obesity and related conditions like type 2 diabetes and cardiovascular disease.
- * Retinoic acid, the active form of vitamin A, and specific proteins involved in vitamin A metabolism, like RBP4 and ALDH1A1, have been linked to these diseases in various studies.
- * The review will analyze both human and rodent studies to explore how vitamin A and its metabolic proteins influence fat cells, fat tissue, and early liver disease, especially non-alcoholic fatty liver disease.*