Metabolic interactions between vitamin A and conjugated linoleic acid

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR- and RXR heterodimer. We also present preliminary data that may position PPAR- at the crossroads between the metabolism of lipids and vitamin

Oceanic eddy‑induced modifications to air–sea heat and CO2 fluxes in the Brazil‑Malvinas Confluence

Sea surface temperature (SST) anomalies caused by a warm core eddy (WCE) in the Southwestern Atlantic Ocean (SWA) rendered a crucial influence on modifying the marine atmospheric boundary layer (MABL). During the first cruise to support the Antarctic Modeling and Observation System (ATMOS) project, a WCE that was shed from the Brazil Current was sampled. Apart from traditional meteorological measurements, we used the Eddy Covariance method to directly measure the ocean–atmosphere sensible heat, latent heat, momentum, and carbon dioxide ( CO2) fluxes. The mechanisms of pressure adjustment and vertical mixing that can make the MABL unstable were both identified. The WCE also acted to increase the surface winds and heat fluxes from the ocean to the atmosphere. Oceanic regions at middle and high latitudes are expected to absorb atmospheric CO2, and are thereby considered as sinks, due to their cold waters. Instead, the presence of this WCE in midlatitudes, surrounded by predominantly cold waters, caused the ocean to locally act as a CO2 source. The contribution to the atmosphere was estimated as 0.3 ± 0.04 mmol m− 2 day− 1, averaged over the sampling period. The CO2 transfer velocity coefficient (K) was determined using a quadratic fit and showed an adequate representation of ocean–atmosphere fluxes. The ocean–atmosphere CO2, momentum, and heat fluxes were each closely correlated with the SST. The increase of SST inside the WCE clearly resulted in larger magnitudes of all of the ocean–atmosphere fluxes studied here. This study adds to our understanding of how oceanic mesoscale structures, such as this WCE, affect the overlying atmosphere

An RBP4 promoter polymorphism increases risk of type 2 diabetes

Aims/hypothesis: Retinol-binding protein 4 (RBP4), originally known for retinol transport, was recently identified as an adipokine affecting insulin resistance. The RBP4 -803GA promoter polymorphism influences binding of hepatic nuclear factor 1α and is associated with type 2 diabetes in case-control studies. We hypothesised that the RBP4 -803GA polymorphism increases type 2 diabetes risk at a population-based level. In addition, information on retinol intake and plasma vitamin A levels enabled us to explore the possible underlying mechanism. Methods: In the Rotterdam Study, a prospective, population-based, follow-up study, the -803GA polymorphism was genotyped. In Cox proportional hazards models, associations of the -803GA polymorphism and retinol intake with type 2 diabetes risk were examined. Moreover, the interaction of the polymorphism with retinol intake on type 2 diabetes risk was assessed. In a subgroup of participants the association of the polymorphism and vitamin A plasma levels was investigated. Results: Homozygous carriers of the -803A allele had increased risk of type 2 diabetes (HR 1.83; 95% CI 1.26-2.66). Retinol intake was not associated with type 2 diabetes risk and showed no interaction with the RBP4 -803GA polymorphism. Furthermore, there was no significant association of the polymorphism with plasma vitamin A levels. Conclusions/interpretation: Our results provide evidence that homozygosity for the RBP4 -803A allele is associated with increased risk of type 2 diabetes in the Rotterdam population. This relationship was not clearly explained by retinol intake and vitamin A plasma levels. Therefore, we cannot differentiate between a retinol-dependent or -independent mechanism of this RBP4 variant

Determination of Vitamin A and its Metabolites in Rat Testis: Possible Involvement of Vitamin A in Testicular Toxicity Caused by Molinate

This study was conducted to evaluate the effect of molinate on retinoids homeostasis in rat testis. Molinate was administrated to male Sprague–Dawley rats (200 mg kg−1 in corn oil, ip). Retinoid measurements were made at 6, 12, 48 and 168 h time points after administration. Testis levels of retinoic acid decreased (32 %) in a statistically significant manner at the 12 and 48 h time points. However, retinol and retinaldehyde were not significantly affected by molinate. These results suggest that molinate affects retinoic acid synthesis in testis and could contribute to understanding the molecular mechanism of molinate involved testicular toxicity

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

BACKGROUND: Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a "second hit" mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. METHODS: We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. RESULTS: First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. CONCLUSION: These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

Insights into the Molecular Mechanisms of the Anti-Atherogenic Actions of Flavonoids in Normal and Obese Mice

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state