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Biomedical subjects

S Wolfram

Publications and source records attributed to S Wolfram.

18 recordsLinked to original sources

Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation.

OBJECTIVE: To examine the antiobesity effect of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol in a mouse model of diet-induced obesity. METHODS: Obesity was induced in male New Zealand black mice by feeding of a high-fat diet. EGCG purified from green tea (TEAVIGO) was supplemented in the diet (0.5 and 1%). Body composition (quantitative magnetic resonance), food intake, and food digestibility were recorded over a 4-week period. Animals were killed and mRNA levels of uncoupling proteins (UCP1-3), leptin, malic enzyme (ME), stearoyl-CoA desaturase-1 (SCD1), glucokinase (GK), and pyruvate kinase (PK) were analysed in different tissues. Also investigated were acute effects of orally administered EGCG (500 mg/kg) on body temperature, activity (transponders), and energy expenditure (indirect calorimetry). RESULTS: Dietary supplementation of EGCG resulted in a dose-dependent attenuation of body fat accumulation. Food intake was not affected but faeces energy content was slightly increased by EGCG, indicating a reduced food digestibility and thus reduced long-term energy absorption. Leptin and SCD1 gene expression in white fat was reduced but SCD1 and UCP1 expression in brown fat was not changed. In liver, gene expression of SCD1, ME, and GK was reduced and that of UCP2 increased. Acute oral administration of EGCG over 3 days had no effect on body temperature, activity, and energy expenditure, whereas respiratory quotient during night (activity phase) was decreased, supportive of a decreased lipogenesis and increased fat oxidation. CONCLUSIONS: Dietary EGCG attenuated diet-induced body fat accretion in mice. EGCG apparently promoted fat oxidation, but its fat-reducing effect could be entirely explained by its effect in reducing diet digestibility.

Animals↗

The impact of different flavonoid classes on colonic CI- secretion in rats.

The plant polyphenol quercetin was shown to induce a significant CI- secretion in intestinal epithelium. In order to elucidate the structural requirements of quercetin and related flavonoids for this activity, we tested the ability of further flavonols and other flavonoids found in edible plants to induce CI- secretion which was measured as an increase in short-circuit current (I(SC)) in rat colon. Whereas several flavonols and the flavon luteolin increased I(SC), other flavonoids such as flavanones, flavans, flavanols, and anthocyanidins failed to do so. Two glycosides of quercetin, spiraeosid, and isoquercitrin, as well as two methoxylated quercetin metabolites, isorhamnetin and tamarixetin, were also able to increase I(SC). We conclude that a 2,3-double bond in conjunction with the 4-oxo group in the C ring and a hydroxylated B ring are necessary for the secretory activity of flavonoids. This activity requires different structural features than those mandatory for the antioxidative properties of flavonoids. Glucosidation and methoxylation of several hydroxyl groups does not necessarily abolish the secretory potential.

Animals↗

Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching.

Fibroblast growth factor (FGF)-1 plays important roles during myocardial and coronary morphogenesis. FGF-1 is also involved in the physiological response of the adult heart against ischemia, which includes cardiomyocyte protection and vascular growth. In the present study, we have generated transgenic mice with specific myocardial overexpression of the gene. Transgene expression was verified by Northern blot, and increased FGF-1 protein content was assessed by Western blot and immunoconfocal microscopy. Anatomic, histomorphological, and ultrastructural analyses revealed no major morphological or developmental abnormalities of transgenic hearts. Capillary density was unaltered, whereas the density of coronary arteries, especially arterioles, was significantly increased, as was the number of branches of the main coronary arteries. In addition, the coronary flow was significantly enhanced in transgenic mice ex vivo. These differences in the anatomic pattern of the coronary vasculature are established during the second month of postnatal life. The present findings demonstrate an important role of FGF-1 in the differentiation and growth of the coronary system and suggest that it is a key regulatory molecule of the differentiation of the arterial system.

Animals↗

Selective interactions among the multiple connexin proteins expressed in the vertebrate lens: the second extracellular domain is a determinant of compatibility between connexins.

Gap junctions are collections of intercellular channels composed of structural proteins called connexins (Cx). We have examined the functional interactions of the three rodent connexins present in the lens, Cx43, Cx46, and Cx50, by expressing them in paired Xenopus oocytes. Homotypic channels containing Cx43, Cx46, or Cx50 all developed high conductance. heterotypic channels composed of Cx46 paired with either Cx43 or Cx50 were also well coupled, whereas Cx50 did not form functional channels with Cx43. We also examined the functional response of homotypic and heterotypic channels to transjunctional voltage and cytoplasmic acidification. We show that all lens connexins exhibited sensitivity to cytoplasmic acidification as well as to voltage, and that voltage-dependent closure of heterotypic channels for a given connexin was dramatically influenced by its partner connexins in the adjacent cell. Based on the observation that Cx43 can discriminate between Cx46 and Cx50, we investigated the molecular determinants that specify compatibility by constructing chimeric connexins from portions of Cx46 and Cx50 and testing them for their ability to form channels with Cx43. When the second extracellular (E2) domain in Cx46 was replaced with the E2 of Cx50, the resulting chimera could no longer form heterotypic channels with Cx43. A reciprocal chimera, where the E2 of Cx46 was inserted into Cx50, acquired the ability to functionally interact with Cx43. Together, these results demonstrate that formation of intercellular channels is a selective process dependent on the identity of the connexins expressed in adjacent cells, and that the second extracellular domain is a determinant of heterotypic compatibility between connexins.

Amino Acid Sequence↗

Na+-gradient dependence of basic amino acid transport into rat intestinal brush border membrane vesicles.

Uptake of L-arginine and L-lysine into brush border membrane (BBM) vesicles from rats fed either a high protein (HP) or a high carbohydrate (HC) diet was studied under conditions of a transmembrane Na+-gradient (Na+out greater than Na+in) or a Na+-equilibrium (Na+out = Na+in). The Na+-gradient caused a stronger stimulation of basic amino acid transport across the BBM in group HP than in group HC. Replacing Cl- as counter ion of Na+ by SCN- in the Na+-gradient experiments did not affect L-lysine uptake. In one series of experiments inhibitory effects of several amino acids and D-glucose on Na+-gradient-dependent L-arginine transport into BBM vesicles were tested. L-Lysine showed the strongest inhibition of L-arginine uptake, but also L-leucine, L-alanine and D-glucose caused a significant decrease of L-arginine uptake into BBM vesicles. The main conclusions are that a transmembrane Na+-gradient is able to energize the transport of basic amino acids across the intestinal BBM and that the transport mechanism of the intestinal BBM for basic amino acids adapts to the protein content of the diet.

Amino Acids↗