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Biomedical subjects

D C Lau

Publications and source records attributed to D C Lau.

29 records · Page 2Linked to original sources
PubMed1990

Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat.

Small changes in lipogenic enzyme activity induced by dietary fats of different composition may, over the long term, have significant impact on the development of obesity. We have investigated the effect of high fat diets (45% of calories as fat) on abundance of mRNA encoding fatty acid synthetase (FAS) and glycerophosphate dehydrogenase (GPDH) in male Sprague-Dawley rats. When caloric intake was equal, the relative amount of hepatic FAS mRNA was greater in rats fed a saturated compared to a polyunsaturated fat diet. This difference could not be attributed to diet-induced changes in plasma insulin concentration. However, both fat diets suppressed hepatic FAS mRNA compared to a sucrose diet. Close correlation between FAS specific activity and the relative amount of mRNA suggested that regulation was mainly at a pre-translational level. Adipose tissue FAS mRNA was suppressed by the two fat diets equally while GPDH mRNA was unaffected by dietary composition. Retroperitoneal fat pads were significantly larger in rats fed saturated compared to those fed polyunsaturated fat for 26 weeks. We concluded that dietary saturated fats fail to suppress hepatic de novo lipogenesis as effectively as polyunsaturated fats, which may have implications for the prevention of obesity in humans.

Adipose Tissue↗
PubMed1989

Cyclosporine toxicity on cultured rat microvascular endothelial cells.

The present study was undertaken to study the mechanism of cyclosporine-induced nephrotoxicity and hypertension. Cultured rat microvascular endothelial cells were exposed to cyclosporine for up to six days at one of the following concentrations: 10, 50, 250, and 1000 ng/ml of culture medium. Cyclosporine inhibited endothelial cell replication in a dose-dependent manner; at higher concentrations (250 and 1000 ng/ml), cell replication decreased by as much as 70 to 90% of controls at four and six days post-treatment, with no evidence of increased cell death. Drug-treated endothelial cells revealed abnormal morphological changes such as formation of cytoplasmic vesicles and nucleolar changes. Prostacyclin release by endothelial cells was increased by about threefold with the addition of cyclosporine (P less than 0.01). Indomethacin significantly decreased prostacyclin release by endothelial cells in the presence or absence of cyclosporine (P less than 0.01). Our data suggest that cyclosporine-induced nephrotoxicity may be mediated, at least partly, by the inhibitory influence of cyclosporine on the regenerative response of microvascular endothelial cells to injury, and the resultant alterations in prostacyclin production by these cells.

Animals↗
PubMed1989

Induction of preadipocyte differentiation by mature fat cells in the rat.

In this study we investigated the influence of mature adipocytes, derived from rat adipose tissue, on the replication and differentiation of preadipocytes in primary culture. Mature fat did not inhibit preadipocyte replication within the 6-d period studied. Preadipocyte differentiation, as assessed by both cytoplasmic lipid accretion and an increase in glycerophosphate dehydrogenase (GPDH) activity, was significantly stimulated by the presence of mature fat tissue or isolated adipocytes. The proportion of cells containing visible lipid droplets by oil red O staining was 47 +/- 10 to 58 +/- 10% (depending on the site of origin of the preadipocytes) when cocultured with mature fat compared with less than 1 to 2 +/- 1% when cultured in medium alone, while GPDH activity was 344 +/- 9 compared with 43 +/- 3 nM NADH/min per mg protein, respectively. This effect was not due to release of triacylglycerols from damaged adipocytes. Fatty acids added to the medium promoted lipid accumulation but did not stimulate a rise in GPDH activity. We concluded that mature adipocytes may release factor(s) that promote preadipocyte differentiation (and maturation).

Adipose Tissue↗
PubMed1987

Regional differences in the replication rate of cultured rat microvascular endothelium from retroperitoneal and epididymal fat pads.

Study of the vascular endothelium has been greatly facilitated by the development of specific cell culture systems isolated from various tissues. We report herein a simple method for establishing a propagating cell culture system of microvascular endothelial cells derived from rat adipose tissue. In addition to the characteristic cobblestone appearance on light microscopy, the microvascular endothelial cells in culture also demonstrated the presence of other markers for large vessel endothelia. Electron microscopy revealed endothelium-specific Weibel-Palade bodies and abundant pinocytotic vesicles. Both retroperitoneal and epididymal endothelia demonstrated the presence of factor VIII antigen by immunofluorescent staining and prostacyclin production. Although there was no appreciable morphological difference between cultured retroperitoneal and epididymal microvascular endothelia, the replication rate of the former was significantly higher than that of the latter (P less than .05). Excessive replication of endothelial cells may play a role in the regional differences of adipose tissue mass in an organism.

Adipose Tissue↗
PubMed1987

Release of mitogenic factors by cultured preadipocytes from massively obese human subjects.

In this study, possible paracrine factors in adipose tissue from lean and obese subjects were sought. Conditioned media were prepared by incubation in alpha minimum essential medium of adipocyte precursors derived from lean and massively obese subjects. Adipocyte-precursor-derived conditioned media from the obese stimulated replication of cultured rat perirenal adipocyte precursors by about fourfold over control. The effect of media conditioned by precursors derived from lean subjects was much less evident. The mitogenicity of conditioned media was abolished by trypsin, indicating the protein nature of the mitogenic factor(s). Sephacryl S-200 chromatography of adipocyte-precursor-derived conditioned media from obese subjects revealed one major active fraction with molecular masses in the range of 25,000-40,000. Our results demonstrate that adipocyte precursors derived from massively obese subjects release factors mitogenic on cultured rat adipocyte precursors. These principles may act as paracrine factors contributing to the development of the adipocyte hyperplasia characteristic of massive obesity.

Adipose Tissue↗
PubMed1983

Purification of a pituitary polypeptide that stimulates the replication of adipocyte precursors in culture.

A bovine anterior pituitary polypeptide that stimulates the replication of rat and human adipocyte precursors has been purified. Its Mr is 44 000-53 000 and its isoelectric point is 9.8-10.3. While pituitary basic fibroblast growth factor is equally mitogenic on adipocyte precursors and skin fibroblasts, the polypeptide described here is selectively more active on the precursors. We postulate that this adipocyte growth factor plays a physiological role by modulating the number of adipocyte precursors.

Adipose Tissue↗
PubMed1983

Effects of glucocorticoid hormones on lipid-synthetic enzymes from different adipose tissue regions and from liver.

The regional diversity of adipose tissue is dramatically accentuated in states of glucocorticoid excess, in which certain fat depots expand, while others contract. We have studied the molecular basis of this redistribution by determining the activity of fatty acid synthetase and enzymes catalyzing di- and tri-acylglycerol synthesis, in subcellular fractions from four adipose depots of rats injected with dexamethasone and from interscapular and epididymal adipocyte precursors after addition of either dexamethasone or corticosterone to confluent monolayers in secondary culture. Subcellular fractions from cervical and interscapular adipose tissue, as well as from cultured interscapular precursors, revealed a general increase in specific enzyme activity. The opposite trend was observed for retroperitoneal and epididymal fat tissue, as well as cultured epididymal precursors. Fatty acid synthetase and cytosolic phosphatidate phosphohydrolase appeared to be most responsive. The findings in culture indicate that the regional effects of glucocorticoids are partly independent of other circulating or neural factors. Injections of dexamethasone led to significantly enhanced specific activity of all the lipid-synthetic enzymes assayed in subcellular fractions from liver. Differences in hormonal influences between liver and certain fat tissue regions represent tissue specificity. In addition, the diverse effects of glucocorticoids on various adipose tissue depots indicate regional or "intratissue" specificity.

Acyltransferases↗
PubMed1981

Exaggerated replication in culture of adipocyte precursors from massively obese persons.

The characteristics of omental adipocyte precursors from massively obese patients, whose average body weights were 231% (range 70--369) of reference values, were studied in propagating culture. When compared to cells from lean subjects, the adipocyte precursors from 34 massively obese patients replicated at a significantly higher rate (p less than 0.001). Excessive replication persisted throughout the first five subcultures. Thus, this characteristic is inherent in the cells, and may reflect the operation of genetic factors in this subgroup of the obese population.

Adipose Tissue↗