Modulation of lipid synthesis,apolipoprotein biogenesis,and lipoprotein assembly by butyrate

Short-chain fatty acids (SCFAs) are potent modulators of the growth, function, and differentiation of intestinal epithelia. In addition, high-fiber diets may protect against the development of atherosclerosis because of their cholesterol-lowering effects due, in large part, to SCFA production, liver sterol metabolism, and bile acid excretion. Although the small gut plays a major role in dietary fat transport and contributes substantially to plasma cholesterol and lipoprotein homeostasis, the impact of SCFAs on intestinal lipid handling remains unknown. In the present study, the modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein secretion by butyrate was investigated in Caco-2 cells plated on permeable polycarbonate filters, which permit separate access to the upper and lower compartments of the monolayers. Highly differentiated and polarized cells (20 days of culture) were incubated for 20 h with 20 mM butyrate in the apical medium. In the presence of [14C]oleic acid, butyrate led to a significant reduction of secreted, labeled triglycerides (27%; P < 0.01) and phospholipids (25%; P < 0.05). Similarly, butyrate significantly decreased the incorporation of [14C]acetate into exported cholesteryl ester (49%; P < 0.005). As expected from these results, with [14C]oleic acid as a precursor, butyrate significantly (P < 0.05) diminished the delivery of radiolabeled chylomicrons and very low-density lipoproteins. In parallel, [35S]methionine pulse labeling of Caco-2 cells revealed the concomitant inhibitory effect of butyrate on the synthesis of apolipoproteins B-48 (28%; P < 0.05) and A-I (32%; P < 0.01). Collectively, our data indicate that butyrate may influence lipid metabolism in Caco-2 cells, thus suggesting a potential regulation of intestinal fat absorption and circulating lipoprotein concentrations.     

Expression of leptin and its receptor in the murine ovary: possible role in the regulation of oocyte maturation

Leptin is a product of the ob gene that is produced primarily by adipose tissue. Leptin and its receptors are found within the ovary, but it is unclear what function this hormone has in the ovary. Using immunohistochemistry, we determined that leptin is found in most cell types in the murine ovary, with the highest staining levels observed in the oocyte. Leptin receptor was also expressed in all of the main ovarian cell types, with the thecal cell layer exhibiting the highest staining levels. Leptin administration did not affect spontaneous or induced maturation of either isolated denuded oocytes or cumulus-oocyte complexes, but it did significantly increase the rate of meiotic resumption in preovulatory follicle-enclosed oocytes (P < 0.01). Measurements of cAMP within oocytes cultured with leptin showed that this enhanced ability to resume meiosis does not occur via activation of phosphodiesterase 3B and subsequent cAMP reduction. These results provide evidence that leptin affects oocyte maturation when the oocyte is cultured within its normal follicular environment. It is suggested that leptin may induce the production of another factor, possibly from thecal cells, that directly or indirectly acts on the oocyte to initiate germinal vesicle breakdown in this species.     

Phylogeny and evolution of calcareous sponges: monophyly of calcinea and calcaronea,high level of morphological homoplasy,and the primitive nature of axial symmetry

Because calcareous sponges are triggering renewed interest with respect to basal metazoan evolution, a phylogenetic framework of their internal relationships is needed to clarify the evolutionary history of key morphological characters. Morphological variation was scored at the suprageneric level within Calcispongia, but little phylogenetic information could be retrieved from morphological characters. For the main subdivision of Calcispongia, the analysis of morphological data weakly supports a classification based upon cytological and embryological characters (Calcinea/Calcaronea) rather than the older classification scheme based upon the aquiferous system (Homocoela/Heterocoela). The 18S ribosomal RNA data were then analyzed, both alone and in combination with morphological characters. The monophyly of Calcispongia is highly supported, but the position of this group with respect to other sponge lineages and to eumetazoan taxa is not resolved. The monophyly of both Calcinea and Calcaronea is retrieved, and the data strongly rejected the competing Homocoela/Heterocoela hypothesis. The phylogeny implies that characters of the skeleton architecture are highly homoplastic, as are characters of the aquiferous system. However, axial symmetry seems to be primitive for all Calcispongia, a conclusion that has potentially far-reaching implications for hypotheses of early body plan evolution in Metazoa.     

Towards an e-biology of ageing: integrating theory and data

Ageing is a highly complex process; it involves interactions between numerous biochemical and cellular mechanisms that affect many tissues in an organism. Although work on the biology of ageing is now advancing quickly, this inherent complexity means that information remains highly fragmented. We describe how a new web-based modelling initiative is seeking to integrate data and hypotheses from diverse biological sources.     

Vascular leak syndrome of Sprague-Dawley rats in a mandibular distraction osteogenesis study

Vascular leak syndrome (VLS) is a common and often fatal sequela of multiple bone traumas, and of infectious, toxic, and allergic insults in human patients. Although an animal model for VLS has not been fully established, rats have shown sensitivity to the syndrome that approximates that of the human population. We describe cases of VLS in three-month-old adult and one-month-old Sprague-Dawley rats in an osteogenesis study aimed at optimizing correction of bone hypoplasias and other craniofacial deformities in children, using a mandibular distraction device. In the study reported here, VLS was diagnosed in 40% of the rats that were necropsied after dying or being euthanized early, subsequent to mandibular osteotomy, a procedure that involves minimal bone trauma. The gross and histologic findings, as well as the clinical course of VLS in the rats of the osteogenesis study, were similar to those of documented human cases. Hence, the rat may be a useful animal model to h elp characterize the physiologic and molecular events that accompany this syndrome.     

Lack of enhanced spinal regeneration in Nogo-deficient mice

The failure of regeneration of severed axons in the adult mammalian central nervous system is thought to be due partly to the presence of endogenous inhibitors of axon regeneration. The nogo gene encodes three proteins (Nogo-A, -B, and -C) that have been proposed to contribute to this inhibition. To determine whether deletion of nogo enhances regenerative ability, we generated two lines of mutant mice, one lacking Nogo-A and -B but not -C (Nogo-A/B mutant), and one deficient in all three isoforms (Nogo-A/B/C mutant). Although Nogo-A/B-deficient myelin has reduced inhibitory activity in a neurite outgrowth assay in vitro, tracing of corticospinal tract fibers after dorsal hemisection of the spinal cord did not reveal an obvious increase in regeneration or sprouting of these fibers in either mouse line, suggesting that elimination of Nogo alone is not sufficient to induce extensive axon regeneration.