Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Essential fatty acid (EFA) deficiency in mice decreases plasma triglyceride (TG) concentrations and increases hepatic TG content. We evaluated in vivo and in vitro whether decreased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) contributes to this consequence of EFA deficiency. EFA deficiency was induced in mice by feeding an EFA-deficient (EFAD) diet for 8 wk. Hepatic VLDL secretion was quantified in fasted EFAD and EFA-sufficient (EFAS) mice using the Triton WR-1339 method. In cultured hepatocytes from EFAD and EFAS mice, VLDL secretion into medium was measured by quantifying [(3)H]-labeled glycerol incorporation into TG and phospholipids. Hepatic expression of genes involved in VLDL synthesis and clearance was measured, as were plasma activities of lipolytic enzymes. TG secretion rates were quantitatively similar in EFAD and EFAS mice in vivo and in primary hepatocytes from EFAD and EFAS mice in vitro. However, EFA deficiency increased the size of secreted VLDL particles, as determined by calculation of particle diameter, particle sizing by light scattering, and evaluation of the TG-to-apoB ratio. EFA deficiency did not inhibit hepatic lipase and lipoprotein lipase activities in plasma, but increased hepatic mRNA levels of apoAV and apoCII, both involved in control of lipolytic degradation of TG-rich lipoproteins. EFA deficiency does not affect hepatic TG secretion rate in mice, but increases the size of secreted VLDL particles. Present data suggest that hypotriglyceridemia during EFA deficiency is related to enhanced clearance of altered VLDL particles.     

Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation

Essential fatty acid (EFA) deficiency induces fat malabsorption, but the pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary phospholipids affect dietary fat solubilization and chylomicron formation, respectively. We investigated whether altered biliary BS and/or phospholipid secretion mediate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing (EFA(+)) or EFA-deficient (EFA(-)) chow for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were determined. Identical dietary experiments were performed in multidrug resistance gene-2-deficient [Mdr2((-/-))] mice, secreting phospholipid-free bile. After 8 wk, EFA(-)-fed wild-type [Mdr2((+/+))] and Mdr2((-/-)) mice were markedly EFA deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio >0.2]. Fat absorption decreased (70.1 +/- 4.2 vs. 99.1 +/- 0.3%, P < 0.001), but bile flow and biliary BS secretion increased in EFA(-) mice compared with EFA(+) controls (4.87 +/- 0.36 vs. 2.87 +/- 0.29 microl x min(-1) x 100 g body wt(-1), P < 0.001, and 252 +/- 30 vs. 145 +/- 20 nmol x min(-1) x 100 g body wt(-1), P < 0.001, respectively). BS composition was similar in EFA(+)- and EFA(-)-fed mice. Similar to EFA(-) Mdr2((+/+)) mice, EFA(-) Mdr2((-/-)) mice developed fat malabsorption associated with twofold increase in bile flow and BS secretion. Fat malabsorption in EFA(-) mice is not due to impaired biliary BS or phospholipid secretion. We hypothesize that EFA deficiency affects intracellular processing of dietary fat by enterocytes.     

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr-/-CAM and cftr+/+CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr-/-CAM mice, DeltaF508/DeltaF508 mice, and littermate controls. EFA metabolism was measured by 13C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr-/-CAM mice, DeltaF508/DeltaF508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13C-enriched in cftr-/-CAM and cftr+/+CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr-/-CAM and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr-/-CAM mice and littermate controls, but consistently higher than in age- and diet-matched C57Bl/6 wild types. We conclude that cftr-/-CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background.     

Effect of essential fatty acid deficiency on G-proteins, cAMP-dependent protein kinase activity and mucin secretion in the rat submandibular salivary glands

Studies were conducted to determine whether β-adrenergic cell signalling is altered in submandibular salivary glands (SMSG) is essential fatty acid (EFA) deficiency. Three groups of rats were fed diets which were deficient in EFA (EFAD), marginally deficient in EFA (MEFAD) or contained sufficient amount of EFA (Control). Rats were killed after 20 wk on diets, SMSG were dissected out and cyclic AMP-dependent protein kinase (PKA) activity was measured. The specific enzyme activities were higher in the homogenates and supernatant fractions of the gland from EFAD and MEFAD rats compared with the controls. The relative levels of guanine nucleotide-binding regulatory proteins (Gs and Gi) were also measured in the SMSG membranes of rats fed the 3 diets. The levels of Gs were significantly higher in the EFAD and MEFAD groups than in the controls. No significant differences were observed in the secretion of trichloroacetic acid-phosphotungstic acid (TCA-PTA) precipitable glycoproteins from the SMSG slices among the 3 dietary groups.     

Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice

Biliary phospholipids (PL) stimulate dietary fat absorption by facilitating intraluminal lipid solubilization and by providing surface components for chylomicron (CM) assembly. Impaired hepatic PL availability induces secretion of large very-low-density lipoproteins, but it is unclear whether CM size depends on biliary PL availability. Biliary PL secretion is absent in multidrug resistance protein 2-deficient (Mdr2(-/-)) mice, whereas it is strongly increased in essential fatty acid (EFA)-deficient mice. We investigated lymphatic CM size and composition in mice with absent (Mdr2(-/-)) or enhanced (EFA deficient) biliary PL secretion and in their respective controls under basal conditions and during enteral lipid administration. EFA deficiency was induced by feeding mice a high-fat, EFA-deficient diet for 8 wk. Lymph was collected by mesenteric lymph duct cannulation with or without intraduodenal lipid administration. Lymph was collected in 30-min fractions for up to 4 h, and lymphatic lipoprotein size was determined by dynamic light-scattering techniques. Lymph lipoprotein subfractions were isolated by ultracentrifugation, and lipid composition was measured. Lymphatic CMs were significantly larger in Mdr2(-/-) mice than in Mdr2(+/+) controls either without (+50%) or with (+25%) enteral lipid administration, and molar core-surface ratios were increased [triglyceride (TG)-to-PL ratio: 4.4 +/- 1.4 in Mdr2(-/-) mice vs. 2.7 +/- 0.8 in Mdr2(+/+) mice, P < 0.001]. In contrast, EFA-deficient mice secreted lipoproteins into lymph that were significantly smaller than in EFA-sufficient controls (173 +/- 32 vs. 236 +/- 47 nm), with correspondingly decreased core-surface ratios (TG-to-PL ratio: 3.0 +/- 1.0 in EFA-deficient mice vs. 6.0 +/- 1.9 in EFA-sufficient mice, P < 0.001). CM size increased during fat absorption in both EFA-deficient and EFA-sufficient mice, but the difference between the groups persisted. In conclusion, the present results strongly suggest that the availability of biliary PL is a major determinant of the size of intestinally produced lipoproteins both under basal conditions and during lipid absorption. Altered CM size may have physiological consequences for postprandial CM processing.     

Essential fatty acid deficiency affects the fatty acid composition of the rat small intestinal and colonic mucosa differently

The intestinal mucosal fatty acid (FA) composition was investigated in Sprague-Dawley rats after 7 and 23 weeks on an isocaloric diet with qualitatively different essential fatty acid (EFA) composition. For comparison, serum and red blood cell (RBC) membranes were investigated in parallel. The molar percentage of most FAs differed significantly between serum and RBC membranes both in controls and rats fed an EFA deficient (EFAD) diet. The influence of the EFA diet was similar on serum and RBC membrane phospholipids except for arachidonic acid (AA) which was more markedly decreased in serum than in RBC membranes. The FA composition was similar in ileal and colonic mucosa, markedly differing from the jejunal mucosa, in which the AA concentration was lower (13.0+/-0.8 versus 16.8+/-0.5 and 15. 7+/-2.8 mol%) and the linoleic acid (LA) concentration higher (34. 0+/-1.6 versus 17.8+/-1.3 and 15.5+/-2.8 mol%, respectively). The EFAD diet induced a more than five-fold decrease in the jejunal and ileal concentration of LA from 33.9+/-1.6 to 6.0+/-1.5 mol% and 17. 8+/-1.3 to 2.1+/-0.7 mol%, respectively. AA decreased more in the ileal and colonic mucosa than in the jejunum. The changes in the FA composition of the intestinal compartments after EFAD diet were different from that in serum and RBC membranes, and did not further change after 23 weeks compared to 7 weeks after introduction of the diet. The study shows that dietary influences are tissue specific and serum or RBC membranes do not mirror local changes in any of the different intestinal segments.     

The possible role of essential fatty acids in the pathophysiology of malnutrition: a review

Biochemical evidence of essential fatty acid deficiency (EFAD) may exist in protein-energy malnutrition (PEM). EFAD is characterised by low 18:2omega6, often in combination with low 20:4omega6 and 22:6omega3, and high 18:1omega9 and 20:3omega9. Some PEM symptoms, notably skin changes, impaired resistance to infections, impaired growth rate and disturbed development may at least partly be explained by EFAD. One or more of the following factors could induce EFAD in PEM: low EFA intake, poor lipid digestion, absorption, transport, desaturation and increased EFA beta-oxidation and peroxidation. EFAD may perpetuate itself by decreasing lipid absorption and transport, and aggravate PEM by impairing nutrient absorption and dietary calorie utilisation. Micronutrient deficiencies may contribute to the impaired EFA bioavailability and metabolism. Nutritional rehabilitation strategies in PEM may consider adequate intakes of EFA and micronutrients, e.g. by promoting breastfeeding. More research is required to gain detailed insight into the role of EFAD in PEM.     

Postnatal essential fatty acid deficiency in mice affects lipoproteins, hepatic lipids, fatty acids and mRNA expression

We have previously reported that essential fatty acid deficiency (EFAD) during suckling in mice resulted in an adult lean phenotype and a resistance to diet-induced obesity. We now hypothesized that postnatal EFAD would cause long-term effects on lipid metabolism. C57BL/6 mice were fed an EFAD or a control diet from the 16th day of gestation and throughout lactation. The pups were weaned to standard diet (STD) and at 15 weeks of age given either high fat diet (HFD) or STD. Lipoprotein profiles, hepatic lipids, fatty acids and mRNA expression were analyzed in 3-week-old and 25-week-old offspring. At weaning, the EFAD pups had higher cholesterol levels in both plasma and liver and 6-fold higher concentrations of hepatic cholesterol esters than control pups. Adult EFAD offspring had higher levels of hepatic cholesterol and linoleic acid, but lower levels of dihomo-γ-linolenic acid and Pparg mRNA expression in the liver. In addition, HFD fed EFAD offspring had lower plasma total cholesterol, lower hepatic triglycerides and lower liver weight compared to controls fed HFD. In conclusion, early postnatal EFAD resulted in short-term alterations with increased hepatic cholesterol accumulation and long-term protection against diet-induced liver steatosis and hypercholesterolemia.     

The influence of dietary essential fatty acids on uterine C20 and C22 fatty acid composition.

The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition.     

N-3 Long-Chain Polyunsaturated Fatty Acid Supplementation Significantly Reduces Liver Oxidative Stress in High Fat Induced Steatosis

Omega-3 (n-3) long-chain polyunsaturated fatty acids (n-3 LCPUFA) are associated with several physiological functions, suggesting that their administration may prevent non transmissible chronic diseases. Therefore, we investigate whether dietary n-3 LCPUFA supplementation triggers an antioxidant response preventing liver steatosis in mice fed a high fat diet (HFD) in relation to n-3 LCPUFA levels. Male C57BL/6J mice received (a) control diet (10% fat, 20% protein, 70% carbohydrate), (b) control diet plus n-3 LCPUFA (108 mg/kg/day eicosapentaenoic acid plus 92 mg/kg/day docosahexaenoic acid), (c) HFD (60% fat, 20% protein, 20% carbohydrate), or (d) HFD plus n-3 LCPUFA for 12 weeks. Parameters of liver steatosis, glutathione status, protein carbonylation, and fatty acid analysis were determined, concomitantly with insulin resistance and serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels. HFD significantly increased total fat and triacylglyceride contents with macrovesicular steatosis, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum TNF-α, IL-1β, and IL-6. Reduced and total liver glutathione contents were diminished by HFD, with higher GSSG/GSH ratio and protein carbonylation, n-3 LCPUFA depletion and elevated n-6/n-3 ratio over control values. These changes were either reduced or normalized to control values in animals subjected to HFD and n-3 LCPUFA, with significant increased hepatic total n-3 LCPUFA content and reduced n-6/n-3 ratio being observed after n-3 LCPUFA supplementation alone. So, repletion of liver n-3 LCPUFA levels by n-3 LCPUFA dietary supplementation in HFD obese mice reduces hepatic lipid content, with concomitant antioxidant and anti-inflammatory responses favouring insulin sensitivity.     

Essential fatty acids in erythrocyte phospholipids during pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids

Evidence that the essential fatty acid (EFA) status during pregnancy and at birth may not be optimal is mainly based on fatty acid profiles of maternal and neonatal plasma phospholipids. However, erythrocyte phospholipids may be more reliable than plasma phospholipids to reflect the EFA status of an individual. Therefore, the present study compares the levels of EFA and of their derivatives (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and at delivery of 184 women and of their infants at birth. In general, the relative concentrations of erythrocyte and plasma phospholipid fatty acids (% of total fatty acids) were strongly correlated, but not at early pregnancy. The overall changes in fatty acid concentrations during pregnancy were qualitatively comparable between erythrocytes and plasma, although the comparability became less towards the end of pregnancy. The changes in absolute amounts (mg/l) of fatty acids in erythrocyte and plasma phospholipids also compare quite well till 32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in relative fatty acid concentrations are qualitatively comparable for erythrocyte and plasma phospholipids. However, significant differences were observed for the absolute amounts of arachidonic and docosahexaenoic acids. No matter these differences, plasma and erythrocyte phospholipids seem equally suitable to reliably quantify the more functional EFA and LCPUFA status based on fatty acid ratios. Correlations between neonatal and maternal fatty acid values at delivery/birth are highly significant in erythrocyte as well as plasma phospholipids. Neonatal erythrocyte (but not plasma) values also correlated strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of maternal erythrocyte phospholipids at early pregnancy.     

Influence of Dietary Conjugated Linoleic Acid and Fat Source on Body Fat and Apoptosis in Mice*

Objective: To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)‐induced body fat loss or DNA fragmentation. Research Methods and Procedures: Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. Results: The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA‐fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA‐fed mice did not differ in body fat compared with FO‐fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA‐supplemented mice and was not affected by fat source. Discussion: Reductions in linoleic acid concentration made mice more sensitive to CLA‐induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA‐induced DNA fragmentation.     

Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c

Nonalcoholic fatty liver disease is characterized by an abnormal accumulation of triacylglycerides in the liver in absence of significant alcohol consumption. Under these conditions, it has been observed an impaired bioavailability of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFAs). The aim of this study was to test the reversion of the prosteatotic and proinflammatory effects of high-fat diet (HFD) in the mouse liver by changing to normocaloric diet and n-3 LCPUFA supplementation. Male C57BL/6J mice were given either control diet (CD) or HFD for 12 weeks. Control and HFD groups were divided into subgroups that continue with CD or subjected to CD plus n-3 LCPUFA for 8 additional weeks. After this time, blood and liver samples were taken and metabolic, morphologic, oxidative stress, inflammatory and signaling parameters were analyzed. The dietary change from HFD to a normocaloric diet with n-3 LCPUFA supplementation significantly reduced insulin resistance and liver steatosis when compared to switching HFD to normocaloric diet alone. In addition, HFD-induced increases in adiposity, adipocyte enlargement and liver oxidative stress and inflammatory cytokine expression were suppressed by n-3 LCPUFA to control values. Importantly, n-3 LCPUFA supplementation abolish HFD-induced enhancement in hepatic SREBP-1c/PPAR-α ratios, suggesting a change in the metabolic status of the liver from a lipogenic condition to one favoring fatty acid oxidation and steatosis attenuation. These findings may provide the rational basis for the use of normocaloric diets supplemented with n-3 LCPUFA in patients with liver steatosis.     

Dietary conjugated linoleic acid alters long chain polyunsaturated fatty acid metabolism in brain and liver of neonatal pigs

Effects of dietary conjugated linoleic acid (CLA, 1% mixed isomers) on n-6 long-chain polyunsaturated fatty acid (LCPUFA) oxidation and biosynthesis were investigated in liver and brain tissues of neonatal piglets. Fatty acid β-oxidation was measured in tissue homogenates using [1-¹⁴C]linoleic acid (LA) and -arachidonic acid (ARA) substrates, while fatty acid desaturation and elongation were traced using [U-¹³C]LA and GC-MS. Dietary CLA had no effect on fatty acid β-oxidation, but significantly decreased n-6 LCPUFA biosynthesis by inhibition of LA elongation and desaturation. Differences were noted between our ¹³C tracer assessment of desaturation/elongation and simple precursor-product indices computed from fatty acid composition data, indicating that caution should be exercised when employing the later. The inhibitory effects of CLA on elongation/desaturation were more pronounced in pigs fed a low fat diet (3% fat) than a high fat diet (25% fat). Direct elongation of linoleic acid to C20:2n-6 via the alternate elongation pathway might play an important role in n-6 LCPUFA synthesis because more than 40% of the synthetic products of [U-¹³C]LA accumulated in [¹³C]20:2n-6. Overall, the data show that dietary CLA shifted the distribution of the synthetic products of [U-¹³C]LA between elongation and desaturation in liver and decreased the total synthetic products of [U-¹³C]LA in brain by inhibiting LA elongation to C20:2n-6. The impact of CLA on brain LCPUFA metabolism of the developing neonate merits consideration and further investigation.     

Mitofusin 2 Protects Hepatocyte Mitochondrial Function from Damage Induced by GCDCA

Mitochondrial impairment is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling and is involved in the development of numerous mitochondrial-related diseases; however, a functional role for Mfn2 in chronic liver cholestasis which is characterized by increased levels of toxic bile acids remain unknown. Therefore, the aims of this study were to evaluate the expression levels of Mfn2 in liver samples from patients with extrahepatic cholestasis and to investigate the role Mfn2 during bile acid induced injury in vitro. Endogenous Mfn2 expression decreased in patients with extrahepatic cholestasis. Glycochenodeoxycholic acid (GCDCA) is the main toxic component of bile acid in patients with extrahepatic cholestasis. In human normal hepatocyte cells (L02), Mfn2 plays an important role in GCDCA-induced mitochondrial damage and changes in mitochondrial morphology. In line with the mitochondrial dysfunction, the expression of Mfn2 decreased significantly under GCDCA treatment conditions. Moreover, the overexpression of Mfn2 effectively attenuated mitochondrial fragmentation and reversed the mitochondrial damage observed in GCDCA-treated L02 cells. Notably, a truncated Mfn2 mutant that lacked the normal C-terminal domain lost the capacity to induce mitochondrial fusion. Increasing the expression of truncated Mfn2 also had a protective effect against the hepatotoxicity of GCDCA. Taken together, these findings indicate that the loss of Mfn2 may play a crucial role the pathogenesis of the liver damage that is observed in patients with extrahepatic cholestasis. The findings also indicate that Mfn2 may directly regulate mitochondrial metabolism independently of its primary fusion function. Therapeutic approaches that target Mfn2 may have protective effects against hepatotoxic of bile acids during cholestasis.     

Developmental changes in the fatty acids of rat uterus and the influence of dietary essential fatty acids.

The effect of age on uterine fatty acid composition was studied in rats fed diets of differing fatty acid composition. Uteri of newly weaned 23-day rats had a higher fatty acid content and a higher proportion of short-chain (less than or equal to C18) fatty acids. Higher incorporation of C less than or equal to 18 fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats compared with adult 240-day rats was detected. Uterine NL incorporated predominantly C less than or equal to 18 fatty acids which may be an important metabolic energy store in developing uterine tissue. Incorporation of C less than or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In contrast, there was selective retention of arachidonic acid (AA) and docosahexanoic acid (DHA) throughout uterine development. An effect of dietary EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked retention of uterine AA when dietary supplies of n-6 EFA were low, but the total AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the three diet groups, and a constant content of AA, EPA and DHA was maintained throughout uterine development, regardless of diet. The degree of n-3 substitution achieved in this study inhibited uterine release of PG and parturition in adult rats.     

Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups

Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. Moreover, suckling pups from dams fed a high fat diet had increased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) deficiency on serum leptin levels in dams and their pups during the suckling period. For the last 10 days of gestation and throughout lactation, pregnant rats were fed a control or an EFA-deficient (EFAD) diet. The levels of leptin and EFA in the serum of the dams and pups were analyzed 1, 2, and 3 weeks after delivery. In parallel, serum levels of glucose and corticosterone were analyzed in the pups. Low serum leptin levels were found in the control lactating dams during the entire lactation period compared with the age-matched nonlactating animals. The leptin concentrations in the lactating dams fed the EFAD diet were lower compared with those fed the control diet. The serum leptin levels of suckling pups from dams on the EFAD diet were markedly decreased compared with controls (P < 0.05). The reduced serum leptin levels could not be explained by nutritional restriction as evaluated by serum levels of glucose and corticosterone. These results indicate the importance of the EFA composition of the maternal diet for serum leptin levels in both dams and pups. EFA deficiency in lactating dams may cause long-term effects on the pups through dysregulation of leptin and leptin-dependent functions. -- Korotkova, M., B. Gabrielsson, L. A. Hanson, and B. Strandvik. Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J. Lipid Res. 2001. 42: 359--365.     

Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice.