Sihem Madani

Implication of acyl chain of diacylglycerols in activation of different isoforms of protein kinase C

We synthesized diacylglycerols (DAGs) containing ω‐6 or ω‐3 polyunsaturated fatty acids [i.e., 1‐stearoyl‐2‐arachidonoyl‐sn‐glycerol (SAG), 1‐stearoyl‐2‐docosahexaenoyL‐sn‐glycerol (SDG), and 1‐stearoyl‐2‐eicosapentaenoyl‐sn‐glycerol (SEG)] and assessed their efficiency on activation of conventional (α, βI, γ) and novel (ε, δ) protein kinase C (PKC). SAG exerted significantly higher stimulatory effects than SDG and SEG on activation of PKCα and PKCδ. Activation of PKCβI by SEG and SDG was higher than that by SAG. Activation of PKCγ did not differ significantly among DAG molecular species. Addition of SAG to assays containing SEG and SDG exerted additive effects on activation of α and ε, but not on βI and γ, isoforms of PKC. SDG‐ and SEG‐induced activation of PKCδ was significantly curtailed by the addition of SAG. Three DAG species significantly curtailed the PMA‐induced activation of βl, γ, and δ, but not of α and ε, isoforms of PKC. Our study demonstrates for the first time that in vitro activation of different PKC isoenzymes vary in response to different DAG species, and one can envisage that this differential regulation may be responsible for their in vivo effects on target organs.—Madani, S., Hichami, A., Legrand, A., Belleville, J., Khan, N. A. Implication of acyl chain of diacylglycerols in activation of different isoforms of protein kinase C. FASEB J. 15, 2595–2601 (2001)

Dietary fish protein lowers blood pressure and alters tissue polyunsaturated fatty acid composition in spontaneously hypertensive rats

OBJECTIVE To investigate the effect of two types of dietary protein on blood pressure, liver fatty acid desaturation and composition, and urine 6-keto-prostaglandin-F (PGF(1alpha)) level, the metabolite of prostacyclin. METHODS 5-wk-old spontaneously hypertensive rats were fed 20% casein or purified fish protein. The fat source was 5% ISIO oil, which contains 47.9% (omega-6) and 1.7% (omega-3) total polyunsaturated fatty acids. After 2 mo on the diet, systolic blood pressure was reduced with fish protein compared with casein (189.8 +/- 10.5 versus 220.7 +/- 8.7). RESULTS Excretion of 6-keto-PGF(1alpha) in urine was negatively correlated with blood pressure. Liver cholesterol and phospholipid concentrations were 1.71- and 1.27-fold lower with fish protein than with casein, respectively. The fish protein diet lowered the 20:4(omega-6) proportion and the ratio of 20:4(omega-6) to 18:2(omega-6) in liver microsomal lipids and phospholipids, which was due to the reduced microsomal Delta6(omega-6) desaturation activity. Dietary protein source did not affect omega-3 fatty acid composition, and this was associated with a similar activation of Delta6(omega-3) desaturation in liver microsomes. CONCLUSIONS The present data indicated a significant blood pressure-lowering effect caused by fish protein, rather than by casein, that modified the fatty acid composition of liver phospholipids and liver microsomal total lipids.

Dietary protein level and origin (casein and highly purified soybean protein) affect hepatic storage, plasma lipid transport, and antioxidative defense status in the rat

The effects of different proportions (10, 20, and 30%) of dietary casein or highly purified soybean protein on lipid metabolism were studied in growing Wistar rats. Hepatic, plasma and lipoprotein lipid, and protein concentrations, plasma thiobarbituric acid-reactive substance (TBARS) levels, and resistance of red blood cells against free-radical attack were determined after a 4-wk dietary regimen. Compared with the 20% casein diet, the 20% soybean protein diet exhibited similar cholesterolemia but lower plasma triacylglycerol concentrations and very-low-density lipoprotein (VLDL) particle number, as measured by diminished contents of VLDL-triacylglycerol, VLDL-protein, and VLDL-apolipoprotein (Apo) B (B-100 and B-48). The soybean protein diet raised high-density lipoprotein (HDL)(2-3) particle number, as measured by enhanced concentrations of HDL(2-3) cholesterol, HDL-phospholipid, and HDL-ApoA-I. Increasing casein or soybean protein level (from 10 to 30%) in the diet involved higher VLDL-ApoB (B-100 and B-48), indicating an increase in the number of VLDL particles. Feeding the 30% casein or 30% soybean protein diet enhanced LDL-HDL(1) cholesterol contents. Despite similar HDL(2-3)-ApoA-I levels, the 30% casein diet enhanced the HDL(2-3) mass and its cholesterol concentrations. In contrast, feeding either the 10 or 30% soybean protein diet significantly lowered HDL(2-3) cholesterol and ApoA-I levels. These effects on cholesterol distribution in lipoprotein fractions occurred despite unchanged total cholesterol concentrations in plasma. Feeding 20% soybean protein versus 20% casein involved lower plasma TBARS concentrations. Decreasing casein or soybean protein levels in the diet were associated with higher plasma TBARS concentrations and had a lower resistance of red blood cells against free-radical attack. The present study shows that dietary protein level and origin play an important role in lipoprotein metabolism and the antioxidative defense status but do not affect total cholesterol concentrations in plasma.

Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers

Abstract The aim of this study was to determine whether macrosomia related to maternal diabetes alters lipoprotein metabolism and whether these abnormalities still persist or regress after 1 month of life. Serum lipoprotein compositions and concentrations as well as serum lipid fatty acid compositions were investigated in macrosomic infants (birth weight = 4840 ± 105 g at term) of insulin-dependent diabetic mothers at birth and after 1 month of life, and were compared to those of control infants (birth weight = 3400 ± 198 g at term) of healthy mothers. Compared to controls, at birth, macrosomic newborns had higher serum lipids, apolipoprotein A-I and B-100, and lipoprotein (very low density lipoprotein, low density lipoprotein, high density lipoprotein-2 and high density lipoprotein-3) levels. Higher percentages of C18:2n-6 in serum triacylglycerols, phospholipids and cholesteryl esters were also observed. At day 30, in macrosomics, serum triacylglycerol, apo B-100, very low density lipoprotein and low density lipoprotein levels were still significantly higher. C18:2n-6 and C18:3n-3 contents in serum phospholipids, triacylglycerols and cholesteryl esters were reduced while C20:4n-6 and C22:6n-3 contents in serum phospholipids and cholesteryl esters were enhanced, compared to control values. Conclusion Macrosomia was associated with alterations in lipoprotein compositions and concentrations at birth, some of which persisted after 1 month of life, and might play a role in the pathogenesis of diabetes and atherosclerosis in adult life.

Impaired lipoprotein metabolism in obese offspring of streptozotocin-induced diabetic rats.

The time course of changes in lipoprotein metabolism of obese offspring of mildly diabetic rats was studied with respect to serum lipoprotein composition as well as LCAT and tissue lipoprotein lipase (LPL) activities. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, obese pups had higher serum glucose, insulin, and lipoprotein (VLDL, LDL-HDL1, HDL2–3) levels than control pups. After 1 mon of life, all of these parameters in obese rats became similar to those of controls. However, LCAT, adipose tissue LPL, and hepatic triacylglycerol lipase activities were high. At 2 mon of age, VLDL-TAG levels were higher in obese females than in controls. By the age of 3 mon, obese offspring had developed insulin resistance with hyperglycemia, hyperinsulinemia, and higher serum lipoprotein concentrations. Indeed, qualitative abnormalities of lipoproteins were seen and were typical of obese and diabetic human beings. Fetal hyperinsulinemia should be considered as a risk factor for later metabolic diseases, including dyslipoproteinemia.