Fatiha Nassir

Effect of selenium deficiency on hepatic lipid and lipoprotein metabolism in the rat

Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.

Magnesium deficiency modulates hepatic lipogenesis and apolipoprotein gene expression in the rat

The present study was performed to determine the effects of magnesium (Mg) deficiency upon plasma lipoproteins and hepatic apolipoprotein gene expression in the rat. The most obvious effect of Mg-deficiency on plasma lipids is a marked increase in post-prandial triacylglycerol concentration. This increased triglyceridemia persists in fasted rats. Density gradient ultracentrifugation analysis revealed marked alterations in the distribution of plasma lipoproteins in Mg-deficient rats. An increase in triacylglycerol-rich lipoproteins (TGRLP) was associated with a significant increase in plasma apolipoprotein B (apo B) concentration and was accompanied by selective accumulation of apo B-48. A decrease in high-density lipoproteins (HDL) was accompanied by a corresponding decrease in plasma apo E concentration and a concordant decrease in hepatic apo E mRNA abundance and biosynthesis. Hepatic apo B-100 synthesis was reduced by over 75% in Mg-deficient animals despite an increase in hepatic apo B mRNA abundance. However, this change in hepatic apo B gene expression was not associated with alterations in posttranscriptional apo B mRNA editing. These changes in apolipoprotein gene expression were associated with increased hepatic lipogenesis, despite the observation that net triacylglycerol secretion rates were not different between Mg-deficient and control animals. Taken together, the data demonstrate a complex pattern of alterations in hepatic lipid metabolism and apolipoprotein gene expression in the Mg-deficient rat and suggest a defect in the catabolism rather than secretion of TGLRP as the major factor underlying the altered plasma lipoprotein profile.

Effects of dietary fermentable fiber on fatty acid synthesis and triglyceride secretion in rats fed fructose-based diet : studies with sugar-beet fiber

Abstract In an attempt to elucidate the role of the dietary fermentable fiber in reduction of hyperlipidemia, we substituted 30% wheat starch with 30% sugar-beet fiber in rats fed a fructose-based (41% fructose), low-fat (2% corn oil) diet. Male Wistar rats ate the test diets for 3 weeks. Feeding the sugar-beet fiber (SBF) diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids compared with rats fed a fiber-free (FF) diet. Feeding SBFdecreased plasma triglyceride and cholesterol concentrations in the postprandial as well as the postabsorptive period. In the liver, triglyceride levels were depressed in concert with the decreased liver lipogenesis and the post-Triton triglyceride secretion. Liver cholesterol levels were unaffected by SBF diet feeding. SBF-fed animals were markedly less fat compared with fiber-free-diet-fed rats. Adipose tissue lipogenesis was depressed in the postprandial period in SBF-fed animals. In short, this study suggests that substitution of easily digested carbohydrates by certain fermentable fibers may play an interesting role in the reduction of hyperlipidemia and obesity.

Hepatic apolipoprotein B synthesis in copper-deficient rats

The present study was designed to examine if induction of apolipoprotein B synthesis is associated with hypercholesterolemia in copper‐deficient rats. This hypercholesterolemia mainly resides in an increase in the HDL‐1 and LDL and is associated with a significant increase in plasma apoB concentration. Liver apoB mRNA levels were not significantly modified in deficient animals as compared to control rats. Studies on liver apolipoprotein synthesis indicated that apoB100 synthesis was increased in deficient animals whereas apoB48 synthesis was unchanged. Thus, it appears that the increase in apoB synthesis in the liver of copper‐deficient rats occurs at the posttranscriptional level. The selective increase in apoB100 synthesis indicates the possible impact of this deficiency on the editing of apoB. An increase in apoB100 synthesis by the liver in copper‐deficient rats may significantly contribute to the increase in plasma concentration of LDL.

Apolipoprotein B gene expression in rat intestine The effect of dietary fiber

The effect of the dietary fiber on apo B mRNA level was studied in the intestine of rats that were fed either fiber‐free or high‐fiber (30% sugar‐beet fiber) low‐fat diets for 3 weeks. The fiber diet studied does not affect jejunal apo B mRNA levels but decreases the level of ileal apo B mRNA. In the rat cecum, in both fiber‐free and fiber groups, we failed to detect the apo B mRNA. The test fiber diet feeding markedly increased fecal bile salt and cholesterol excretions. We suggest that dietary fiber can modify apo B expression in the intestine. The increased fecal bile salt excretion might be involved in such a modification.

Age-related response to dietary fructose in the rat : discrepancy in triglyceride and apolipoprotein B synthesis as a possible mechanism for fatty liver induction in adult rats

Abstract The effects of fructose feeding on plasma and liver lipids, triglyceride secretion, and plasma apolipoprotein B and their liver mRNA level were studied in young and adult rats. We have shown that the responsiveness of adult rats to dietary fructose differs from that of young rats with regard to body parameters as well biochemical analyses. In young rats, fructose diet causes a coupled induction of liver triglyceride and apolipoprotein B synthesis via increased mRNA level. In adult rats it appears that triglyceride secretion is lower and less inducible by dietary fructose than in young rats. This insufficient export of the excess of synthesized triglycerides may cause fatty liver in adult animals. Reduced adaptation of liver lipoprotein secretion to dietary carbohydrates in adult animals may be explained by the failure to stimulate apolipoprotein B synthesis at the mRNA level in these rats.

The effect of dietary copper on rat plasma apolipoprotein B, E plasma levels, and apolipoprotein gene expression in liver and intestine

The plasma levels of apo B and apo E, and the level of hepatic and intestinal mRNA coding for these apolipoproteins were investigated in weanling male rats pair-fed for 6 wk with a control or copperdeficient diet. Plasma cholesterol, triglycerides, and phospholipids were significantly increased, and plasma apo B and apo E levels were also markedly increased in copper-deficient rats as compared to control rats. Copper deficiency significantly increased triglyceride levels and decreased cholesterol levels in the liver. No major differences in the levels of hepatic and intestinal apo B and apo E mRNA occurred between control and copper-deficient rats. These data imply that hypertriglyceridemia dn hypercholesterolemia owing to the copper deficiency are not accompanied by modifications in the gene expression at the mRNA level in the liver and intestine of the apolipoproteins studied.

Apolipoprotein A-I, A-IV and E synthesis in the liver of copper-deficient rats.

Copper deficiency induces hypercholesterolemia in the rat. This hypercholesterolemia is mainly due to an increase in apo E-rich high density lipoproteins (HDL1). The present study was undertaken to determine whether the HDL increase could be explained by altered low-molecular weight apolipoprotein (apo) synthesis in the liver. The effect of copper deficiency on apo A-I, apo A-IV and apo E concentrations in plasma, as well as on respective mRNA levels and synthesis in the liver, were therefore investigated. We observed that the increased HDL1 levels in the plasma of copper-deficient rats were associated with a significant rise in plasma apo E concentrations; however, plasma apo A-I and apo A-IV concentrations remained unchanged. Liver apo synthesis and respective apo mRNA levels were not significantly altered in copper-deficient animals when compared to control rats. No changes in apo E mRNA levels in various tissues from copper-deficient, as compared to control rats, were noted. Based on the data obtained, it was concluded that the observed changes in plasma lipoprotein and apo concentrations are not related to changes in low-molecular weight apo synthesis in the liver. The mechanisms of the impaired catabolism of HDL1 should be further evaluated to possibly explain the observed increase in this fraction in copper-deficient rats.

Increased hepatic synthesis and accumulation of plasma apolipoprotein B100 in copper-deficient rats does not result from modification in apolipoprotein B mRNA editing

Experimentally induced copper deficiency in the rat results in increased plasma apolipoprotein B100 (apo B100) concentration in association with increased hepatic apo B100 synthesis. This enhancement of apo B100 synthesis and plasma accumulation accounts for the rise of plasma low density lipoprotein in these animals. In the present study, we have investigated if the selective increase in hepatic apo B100 synthesis is accounted for by changes in apo B mRNA editing. Reverse transcription coupled with polymerase chain reaction amplification and primer extension analysis of apo B cDNA revealed no differences in apo B mRNA editing in either the liver or small intestine between control and copper-deficient rats. We speculate that the increase in apo B100 synthesis in the liver of copper-deficient rats reflects posttranslational alterations in gene expression accompanying changes in very low density lipoprotein assembly and secretion.

Hypoalbuminaemia in acute phase response is not related to depressed albumin synthesis: experimental evidence in magnesium-deficient rat

Studies conducted on laboratory animals have clearly established that dietary magnesium (Mg) deficiency leads to aninflammatory process, that might participate in pathological consequences of this deficiency. Several alterations in plasma biochemistry have been described in Mg-deficient animals and the pattern appears to relate to the inflammatory acute phase response. The present study provides experimental evidence that acute phase response caused by Mg deficiency in the rat leads to hypoalbuminaemia. Thus underlying mechanism for the observed hypoalbuminaemia in Mg-deficient rats was studied in the present work. Our results show that total protein and albumin syntheses in the liver were not affected by Mg-deficiency. Because the capacity of the liver to synthesize albumin appears to be maintained the observed hypoalbuminaemia could be due to an increase in catabolism or the escape of this protein from the plasma pool in to the extra-vascular space.