Linking soils and human health: geospatial analysis of ground-sampled soil data in relation to community-level podoconiosis data in North West Cameroon.

BACKGROUND: Podoconiosis is a form of leg swelling, which arises when individuals are exposed over time to red clay soil formed from alkaline volcanic rock. The exact causal agent of the disease is unknown. This study investigates associations between podoconiosis disease data and ground-sampled soil data from North West Cameroon. METHODS: The mineralogy and elemental concentrations were measured in the soil samples and the data were spatially interpolated. Mean soil values were calculated from a 3 km buffer region around the prevalence data points to perform statistical analysis. Analysis included Spearman's rho correlation, binary logistic regression and principal component analysis (PCA). RESULTS: Six elements, barium, beryllium, potassium, rubidium, strontium and thallium, as well as two minerals, potassium feldspar and quartz, were identified as statistically related to podoconiosis. PCA did not show distinct separation between the spatial locations with or without recorded cases of podoconiosis, indicating that other factors such as shoe-wearing behaviour and genetics may significantly influence podoconiosis occurrence and prevalence in North West Cameroon. CONCLUSION: Several soil variables were statistically significantly related to podoconiosis. To further the current study, future investigations will look at the inflammatory pathway response of cells after exposure to these variables.

Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.

The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population.

OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.

Synthesis, assembly, and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope.

Syncytin is a fusogenic protein involved in the formation of the placental syncytiotrophoblast layer. This protein is encoded by the envelope gene of the ERVWE1 proviral locus belonging to the human endogenous retrovirus W (HERV-W) family. The HERV-W infectious ancestor entered the primate lineage 25 to 40 million years ago. Although the syncytin fusion property has been clearly demonstrated, little is known about this cellular protein maturation process with respect to classical infectious retrovirus envelope proteins. Here we show that the cellular syncytin protein is synthesized as a glycosylated gPr73 precursor cleaved into two mature proteins, a gp50 surface subunit (SU) and a gp24 transmembrane subunit (TM). These SU and TM subunits are found associated as homotrimers. The intracytoplasmic tail is critical to the fusogenic phenotype, although its cleavage requirements seem to have diverged from those of classical retroviral maturation.

An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor.

A new human endogenous retrovirus (HERV) family, termed HERV-W, was recently described (J.-L. Blond, F. Besème, L. Duret, O. Bouton, F. Bedin, H. Perron, B. Mandrand, and F. Mallet, J. Virol. 73:1175-1185, 1999). HERV-W mRNAs were found to be specifically expressed in placenta cells, and an env cDNA containing a complete open reading frame was recovered. In cell-cell fusion assays, we demonstrate here that the product of the HERV-W env gene is a highly fusogenic membrane glycoprotein. Transfection of an HERV-W Env expression vector in a panel of cell lines derived from different species resulted in formation of syncytia in primate and pig cells upon interaction with the type D mammalian retrovirus receptor. Moreover, envelope glycoproteins encoded by HERV-W were specifically detected in placenta cells, suggesting that they may play a physiological role during pregnancy and placenta formation.

Predictive value of early human chorionic gonadotrophin serum profiles for fetal growth retardation.

The possibility of using first trimester maternal serum human chorionic gonadotrophin (HCG) profiles to predict fetal growth retardation (FGR) was tested in 236 women with singleton pregnancies obtained after in-vitro fertilization (IVF). Pregnancies were monitored by serial analysis (two or more) of serum HCG at at least 48 h intervals. Serum was obtained between the 13th and the 35th day after conception (i.e. on the day of IVF). Early miscarriage occurred in 23.7% and FGR in 10.9% of pregnancies. Serum HCG profiles were higher than the 90th and lower than the 10th percentile in 12.3% and 19.5% of the cases respectively. FGR was significantly more frequent in women with serum HCG profiles lower than the 10th percentile than in women with normal profiles (45.5% versus 7.2%; P < 0.001), with a relative risk of 6.5 (95% confidence interval 2.7-15.6). FGR rates were similar in women with normal and high profiles of serum HCG. Pre-eclampsia and premature delivery rates were similar in women with normal and abnormal profiles of serum HCG. First trimester serum HCG should be further investigated as a potential marker of FGR.

Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family.

The multiple sclerosis-associated retrovirus (MSRV) isolated from plasma of MS patients was found to be phylogenetically and experimentally related to human endogenous retroviruses (HERVs). To characterize the MSRV-related HERV family and to test the hypothesis of a replication-competent HERV, we have investigated the expression of MSRV-related sequences in healthy tissues. The expression of MSRV-related transcripts restricted to the placenta led to the isolation of overlapping cDNA clones from a cDNA library. These cDNAs spanned a 7.6-kb region containing gag, pol, and env genes; RU5 and U3R flanking sequences; a polypurine tract; and a primer binding site (PBS). As this PBS showed similarity to avian retrovirus PBSs used by tRNATrp, this new HERV family was named HERV-W. Several genomic elements were identified, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, as gag and pol open reading frames (ORFs) were interrupted by frameshifts and stop codons. A complete ORF putatively coding for an envelope protein was found both on the HERV-W DNA prototype and within an RU5-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-kb transcripts was observed, and a putative splicing strategy was described. The apparently tissue-restricted HERV-W long terminal repeat expression is discussed with respect to physiological and pathological contexts.

In vitro desaturation or elongation of monotrans isomers of linoleic acid by rat liver microsomes.

Several nutritional studies have shown the in vivo conversion of the 9c, 12t-18:2 and 9t, 12c-18:2 into long chain polyunsaturated fatty acids (PUFA) containing 20 carbons (geometrical isomers of eicosadienoic and eicosatetraenoic acids). In the present work, some in vitro studies were carried out in order to have precise information on the conversion of these two isomers. In a first set of experiments, studies were focused on the in vitro delta6 desaturation, the first regulatory step of the biosynthesis of n-6 long chain PUFA, from 9c, 12c-18:2. Rat liver microsomes were prepared and incubated under desaturation conditions with [1-14C]-9c, 12c-18:2 in presence of unlabelled 9c, 12t-, 9t, 12c- or 9t, 12t-18:2. The data show that each trans isomer induced a decrease of the delta6 desaturation of the [1-14C]-9c, 12c-18:2, but the 9c, 12t-18:2 was the most potent inhibitor (up to 63%). Rat liver microsomes were also incubated with [1-14C]-9c, 12c-18:2, [1-14C]-9c, 12t-18:2 or [1-14C]-9t, 12c-18:2 under desaturation conditions. The results indicated that 18:2 delta9c, 12t is a much better substrate for desaturase than 9t, 12c-18:2. Moreover, the conversion levels of [1-14C]-9c, 12t-18:2 was similar to what was observed for its all cis homologue, at low substrate concentration only. In a second set of experiments, in vitro elongation studies of each mono-trans 18:2 isomer and 9c, 12c-18:2 were carried out. For that purpose, rat liver microsomes were incubated with [1-14C]-9c, 12c-18:2, [1-14C]-9c, 12t-18:2 or [1-14C]-9t, 12c-18:2 underelongation conditions. The data show that [1-14C]-9t, 12c-18:2 is betterelongated than 9c, 12c-18:2 while the amount of product formed from [1-14C]-9c, 12t-18:2 was lower than was produced from the 9c, 12c-18:2. Thus, the desaturation enzymes presented a higher affinity for the 9c, 12t-18:2 whereas the elongation enzyme presented a higher affinity for the 9t, 12c-18:2.

Highly purified soybean protein is not hypocholesterolemic in rats but stimulates cholesterol synthesis and excretion and reduces polyunsaturated fatty acid biosynthesis.

The specific effects of soybean protein on lipid metabolism were determined with highly purified soybean protein. At 5 wk of age, growing rats were fed diets containing 20% highly purified soybean protein or casein supplemented or not with 0.1% cholesterol for 2 mo. Plasma and liver lipid composition, fecal steroid excretion and several hepatic enzyme activities were measured. There were no significant dietary protein-related differences in plasma and liver cholesterol concentrations. When diets were cholesterol free, highly purified soybean protein stimulated fecal neutral and acidic steroid excretion associated with concomitantly higher hydroxy methylglutaryl CoA (HMG-CoA) reductase activity, but lower cholesterol 7alpha-hydroxylase activity. Soybean protein lowered the linoleate desaturation index [20:4(n-6)/18:2(n-6)] in liver microsomal lipids and phospholipids. This may have been due to the reduced microsomal Delta6(n-6) desaturase activity in rats fed soybean protein, whereas Delta5(n-6) desaturase activity did not differ between groups fed the two proteins. Cholesterol supplementation (0.1%) did not affect plasma cholesterol but increased liver cholesterol and triacylglycerol concentrations and reduced HMG-CoA reductase activity; this latter effect was greatest in rats fed soybean protein. Cholesterol 7alpha-hydroxylase activity, however, was diminished only in rats fed casein. Desaturase activities, and particularly Delta5(n-6) activity, were lowered by cholesterol supplementation in rats fed both protein diets, including a significantly lower 20:4(n-6)/18:2(n-6) ratio in liver microsomal lipids and liver phospholipids. Thus although dietary proteins have no effect on serum cholesterol in rats, they affect enzyme activities involved in cholesterol metabolism and fatty acid desaturation.

Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis.

The partial molecular characterization of multiple sclerosis (MS)-associated retrovirus (MSRV), a novel retrovirus previously called LM7, is reported. MSRV has been isolated repeatedly from leptomeningeal, choroid plexus and from Epstein-Barr virus-immortalized B cells of MS patients. A strategy based on reverse transcriptase PCR with RNA-purified extracellular virions yielded an initial pol fragment from which other regions of the retroviral genome were subsequently obtained by sequence extension. MSRV-specific PCR primers amplified a pol region from RNA present at the peak of reverse transcriptase activity, coinciding with extracellular viral particles in sucrose density gradients. The same sequence was detected in noncellular RNA from MS patient plasma and in cerebrospinal fluid from untreated MS patients. MSRV is related to, but distinct from, the endogenous retroviral sequence ERV9. Whether MSRV represents an exogenous retrovirus with closely related endogenous elements or a replication-competent, virion-producing, endogenous provirus is as yet unknown. Further molecular epidemiological studies are required to determine precisely the apparent association of virions containing MSRV RNA with MS.

Conversion of 18:3 delta 9cis, 12cis, 15trans in rat liver microsomes.

Several years ago, it was established that the delta 15 trans isomer of alpha-linolenic acid is converted in vivo into fatty acids containing 20 and 22 carbons (geometrical isomers of eicosapentaenoic and docosahexaenoic acids). The present study focused on the in vitro delta 6 desaturation, the first step of the biosynthesis of the n-3 long-chain polyunsaturated fatty acids from 18:3n-3. For that purpose, rat liver microsomes were prepared and incubated with radiolabeled 18:3 delta 9cis,12cis,15cis (18:3c,c,c) or 18:3 delta 9cis, 12cis, 15trans (18:3c,c,t) under desaturation conditions. The data show that 18:3c,c,t is converted at a lower rate compared with alpha-linolenic acid. The product of conversion of 18:3c,c,t may be 18:4 delta 6cis, 9cis, 12cis, 15trans resulting from a delta 6 desaturation of the trans substrate. Moreover, the conversion of radiolabeled 18:3c,c,t was strongly decreased by the presence of 18:3c,c,c (up to 48%) while the 18:3c,c,t only slightly decreased the conversion of radiolabeled 18:3c,c,c. Thus, the desaturation enzyme presented a higher affinity for the native all-cis n-3 substrate.

Evaluation of maternal plasma creatine kinase activity as a marker of abnormal early pregnancy.

We have tested the value of maternal plasma creatine kinase activity for diagnosing ectopic pregnancies obtained after in-vitro fertilization and embryo transfer. Plasma creatine kinase was assayed in 57 patients: 20 normal, 23 miscarriages and 14 ectopic pregnancies, for a total of 240 samples. All values were in the lower part of the normal range except only one in a miscarrying patient. A statistically significant difference was observed for a cut-off value of 45 IU/l between normal and ectopic pregnancies. However, for this cut-off point, the measurement of plasma creatine kinase activity had a sensitivity of 0.50 and a specificity of 0.76 for the diagnosis of ectopic pregnancy. The positive predictive value was 0.69. Creatine kinase activity measurements are thus of no practical value in this particular population, in which an early and specific marker of ectopic implantation would be of paramount interest. The association of human chorionic gonadotrophin (HCG) determinations and ultrasound scanning of the pelvis still remain the best paraclinical support for an early diagnosis of ectopic implantation.

Effect of low levels of dietary fish oil on fatty acid desaturation and tissue fatty acids in obese and lean rats.

The effect of very low levels of dietary long-chain n-3 fatty acids on delta 6 desaturation of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and on delta 5 desaturation of dihomo-gamma-linolenic acid (20:3n-6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n-3 fatty acids per 100 g of diet were compared to those fed the same amount of alpha-linolenic acid. Low amounts of long-chain n-3 fatty acids greatly inhibited delta 6 desaturation of 18:2n-6 and delta 5 desaturation of 20:3n-6, while delta 6 desaturation of 18:3n-3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids was reflected in a decrease in arachidonic acid (20:4n-6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20:4n-6 during fish oil ingestion. Docosahexaenoic acid (22:6n-3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.

Incorporation of delta 6- and delta 5-desaturation fatty acids in liver microsomal lipid classes of obese Zucker rats fed n - 6 or n - 3 fatty acids.

The aim of this work was to study the effect of dietary n - 6 (as borage oil) and of n - 3 (as fish oil) fatty acids on the incorporation--in liver microsomal lipid classes--of fatty acids involved in delta 6- and delta 5-desaturations in obese Zucker rats compared with their lean littermates and with Wistar control rats. We observed that body and liver weights were decreased when obese Zucker rats were fed the fish oil diet. The major part of the radioactivity was recovered, in the obese Zucker rats, into the neutral lipids and especially into the triacylglycerols, while it was recovered into the phospholipid classes, especially into phosphatidylcholine, in the two other strains. Results show, in all phenotypes, an increased alpha-linolenic acid delta 6-desaturation in PL classes when the rats were fed the fish oil diet. However, a decreased linoleic acid delta 6- and delta 5-desaturation was observed in obese Zucker rats fed the fish oil diet. The fish oil diet favours the n - 3 fatty acid biosynthesis and incorporation into liver microsomal lipid classes to the prejudice of the n - 6 fatty acid series. The fatty acid incorporation is simultaneously regulated by the genetical phenotype and dietary fatty acids.

The metabolism and availability of essential fatty acids in animal and human tissues.

Essential fatty acids (EFA), which are not synthesized in animal and human tissues, belong to the n-6 and n-3 families of polyunsaturated fatty acids (PUFA), derived from linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (LNA, 18:3n-3). Optimal requirements are 3-6% of ingested energy for LA and 0.5-1% for LNA in adults. Requirements in LNA are higher in development. Dietary sources of LA and LNA are principally plants, while arachidonic acid (AA, 20:4n-6) is found in products from terrestrian animals, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in products from marine animals. EFA are principally present in dietary triacylglycerols, which should be hydrolyzed by lipases in gastric and intestinal lumen. DHA seems to be released more slowly than the others. Its intestinal absorption is delayed but not decreased. Long-chain PUFAs are incorporated in noticeable amounts in chylomicron phospholipids. However, their uptake by tissues is no more rapid than uptake of shorter chain PUFA. In tissues, LA and LNA, which constitute the major part of dietary EFA, should be converted into fatty acids of longer and more unsaturated chain by alternate desaturation (delta 6, delta 5, delta 4)-elongation reactions. Animal tissues are more active in this biosynthesis than human tissues. Liver is one of the most active organs and its role is critical in providing less active tissues, particularly the brain, with long-chain PUFA secreted in VLDL (very low density lipoprotein). In liver, many nutritional, hormonal and physiological factors act on the PUFA biosynthesis. Dietary fatty acids exert a great influence and are often inhibitory. Dietary LNA inhibits delta 6 desaturation of LA. The desaturation products AA, EPA, and DHA inhibit delta 6 desaturation of LA and delta 5 desaturation of DGLA (dihomo-gamma-linolenic acid). With regard to hormones, insulin and thyroxin are necessary to delta 6 and delta 5 desaturation activities, whereas other hormones (glucagon, epinephrine, ACTH, glucocorticoids) inhibit desaturation. Concerning the physiological factors, the age of individuals is critical. In the fetus, the liver and the brain are capable of converting LA and LNA into longer-chain EFA, but these are also delivered by the mother, after synthesis in the maternal liver and placenta. Just after birth, in animals, the delta 6 desaturation activity increases in the liver and decreases in the brain. In aging, the capacity of the whole liver to desaturate LA and DGLA is equal at 1.5 and 25 months of age in rats fed a balanced diet throughout their life and the AA and DHA content of tissue phospholipids is unchanged in aging.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of fatty acid delta 6- and delta 5-desaturation by cyclopropene fatty acids in rat liver microsomes.

delta 6-Desaturation of linoleic acid and delta 5-desaturation of dihomo-gamma-linolenic acid were measured in liver microsomes from rats fed fresh Baobab seed oil containing cyclopropene fatty acids (malvalic acid and sterculic acid) or heated Baobab seed oil practically devoid of these fatty acids or control oil. The presence of cyclopropene fatty acids in the fresh Baobab oil diet highly depressed both desaturations, but delta 6- more than delta 5-desaturation. The decreased capacity of microsomes to desaturate was reflected in the lower arachidonic acid content in microsomal phospholipids from rats fed this oil. However it was also lower in rats fed heated oil although in vitro delta 6- and delta 5-desaturation were not depressed. When liver microsomes prepared from rats fed the control diet were used for the desaturation assays, the presence of free malvalic or sterculic acid in the medium, also highly depressed delta 6- and delta 5-desaturation. The incorporation of arachidonic acid, the product of delta 5-desaturation, into phospholipids was also highly depressed, while that of the precursor dihomo-gamma-linolenic acid was not. This suggests that cyclopropene fatty acids specifically inhibit incorporation of the delta 5-desaturation product into phospholipids or that they specifically inhibit desaturation of the substrate previously incorporated into a membrane phospholipid.

Age-related changes in delta 6 and delta 5 desaturase activities in rat liver microsomes.

Age-related changes in delta 6 desaturation of [1-14C]alpha-linolenic acid and [1-14C]linoleic acid and in delta 5 desaturation of [2-14C]dihomo-gamma-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. delta 6 Desaturation of alpha-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-gamma-linolenic acid to arachidonic acid by delta 5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of simvastatin on desaturase activities in liver from lean and obese Zucker rats.

The effect of simvastatin, a hypocholesterolemic drug, on the biosynthesis of arachidonic acid was studied in obese and lean Zucker rats. After administration of 2 mg/kg body weight/d for 13 d, delta 6 and delta 5 desaturase activities were measured in liver microsomes at two substrate concentrations. In untreated rats, the delta 6 desaturation rate was similar in the obese and lean rats when measured at saturating substrate levels, whereas delta 5 desaturation was lower in the obese animals. Treatment with simvastatin did not change delta 6 desaturation in either phenotype but increased delta 5 desaturation in obese rats to reach the unchanged rate observed in lean animals. The changes were not reflected in the fatty acid composition of liver microsomal phospholipids when expressed as micrograms fatty acid/g of liver.