Mitochondrial folate metabolism-mediated α-linolenic acid exhaustion masks liver fibrosis resolution.

Sustainable TGF-ß1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-ß1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis. In activated hepatic stellate cells, folate shifted toward mitochondrial metabolism to sustain TGF-ß1 signaling. Mechanistically, nontargeted metabolomics screening identified that α-linolenic acid (ALA) is exhausted by mitochondrial folate metabolism in activated hepatic stellate cells. Knocking down serine hydroxymethyltransferase 2 increases the bioconversion of ALA to docosahexaenoic acid, which inhibits TGF-ß1 signaling. Finally, blocking mitochondrial folate metabolism promoted liver fibrosis resolution in nonalcoholic steatohepatitis mice. In conclusion, mitochondrial folate metabolism/ALA exhaustion/TGF-ßR1 reproduction is a feedforward signaling to sustain profibrotic TGF-ß1 signaling, and targeting mitochondrial folate metabolism is a promising strategy to enforce liver fibrosis resolution.

Modeled replacement of traditional soybean and canola oil with high-oleic varieties increases monounsaturated fatty acid and reduces both saturated fatty acid and polyunsaturated fatty acid intake in the US adult population.

BACKGROUND: High-oleic (HO) seed oils are being introduced as replacements for trans fatty acid (TFA)-containing fats and oils. Negative health effects associated with TFAs led to their removal from the US Generally Recognized As Safe list. HO oils formulated for use in food production may result in changes in fatty acid intake at population levels. Objectives: The purposes of this study were to 1) identify major food sources of soybean oil (SO) and canola oil (CO), 2) estimate effects of replacing SO and CO with HO varieties on fatty acid intake overall and by age and sex strata, and 3) compare predicted intakes with the Dietary Reference Intakes and Adequate Intakes (AIs) for the essential fatty acids (EFAs) α-linolenic acid (ALA) and linoleic acid (LA). Design: Food and nutrient intakes from NHANES waves 2007-2008, 2009-2010, 2011-2012, and 2013-2014 in 21,029 individuals aged ≥20 y were used to model dietary changes. We estimated the intake of fatty acid with the replacement of HO-SO and HO-CO for commodity SO and CO at 10%, 25%, and 50% and evaluated the potential for meeting the AI at these levels. RESULTS: Each modeling scenario decreased saturated fatty acids (SFAs), although intakes remained greater than recommended for all age and sex groups. Models of all levels increased the intake of total monounsaturated fatty acids (MUFAs), especially oleic acid, and decreased the intake of total polyunsaturated fatty acids (PUFAs), particularly LA and ALA. Replacement of traditional with HO oils at 25-50% places specific adult age and sex groups at risk of not meeting the AI for LA and ALA. Conclusions: The replacement of traditional oils with HO varieties will increase MUFA intake and reduce both SFA and PUFA intakes, including EFAs, and may place specific age and sex groups at risk of inadequate LA and ALA intake.

Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.

The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.

Dietary linoleic acid requirements in the presence of α-linolenic acid are lower than the historical 2 % of energy intake value, study in rats.

Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1-1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.

Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: association with altered 5-HT1A and alpha2A adrenergic receptor expression.

Omega-3 fatty acid deficiency during development leads to enduing alterations in central monoamine neurotransmission in rat brain. Here we investigated the effects of omega-3 fatty acid deficiency on behavioral and neurochemical responses to chronic fluoxetine (FLX) treatment. Male rats were fed diets with (CON, n = 34) or without (DEF, n = 30) the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during peri-adolescent development (P21-P90). A subset of CON (n = 14) and DEF (n = 12) rats were administered FLX (10 mg/kg/d) through their drinking water for 30 d beginning on P60. The forced swimming test (FST) was initiated on P90, and regional brain mRNA markers of serotonin and noradrenaline neurotransmission were determined. Dietary ALA depletion led to significant reductions in frontal cortex docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-26%, p = 0.0001) and DEF + FLX (-32%, p = 0.0001) rats. Plasma FLX and norfluoxetine concentrations did not different between FLX-treated DEF and CON rats. During the 15-min FST pretest, DEF + FLX rats exhibited significantly greater climbing behavior compared with CON + FLX rats. During the 5-min test trial, FLX treatment reduced immobility and increased swimming in CON and DEF rats, and only DEF + FLX rats exhibited significant elevations in climbing behavior. DEF + FLX rats exhibited greater midbrain, and lower frontal cortex, 5-HT1A mRNA expression compared with all groups including CON + FLX rats. DEF + FLX rats also exhibited greater midbrain alpha2A adrenergic receptor mRNA expression which was positively correlated with climbing behavior in the FST. These preclinical data demonstrate that low omega-3 fatty acid status leads to abnormal behavioral and neurochemical responses to chronic FLX treatment in male rats.

A dairy fat matrix providing alpha-linolenic acid (ALA) is better than a vegetable fat mixture to increase brain DHA accretion in young rats.

Achieving an appropriate DHA status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how alpha-linolenic acid (ALA), provided for six weeks after weaning by different dietary fat matrix, improved brain DHA content of young male rats born from deficient-dams. The level of ALA achieved was based on the fat composition of usual infant vegetable formula. A palm oil-blend diet thus providing 1.5%ALA was compared to dairy fat-blend-based diets that provided either 1.5%ALA or 2.3%ALA, or a rapeseed oil diet providing 8.3%ALA (n-6/n-3 ratio were, respectively 10,10,5,2.5). The 1.5%ALA-dairy-fat-blend was superior to 1.5%ALA-palm-oil-blend to restore values of brain DHA, while the 2.3%ALA-dairy-fat-blend exhibited a further increase and reached the values obtained with pure rapeseed diet (8.3%ALA). Dairy-fat-blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of post-weaning rats. Providing dairy fat as well as a reduction of the LA/ALA ratio should be reconsidered to design infant formula.

Regulation of rat brain polyunsaturated fatty acid (PUFA) metabolism during graded dietary n-3 PUFA deprivation.

Knowing threshold changes in brain lipids and lipid enzymes during dietary n-3 polyunsaturated fatty acid deprivation may elucidate dietary regulation of brain lipid metabolism. To determine thresholds, rats were fed for 15 weeks DHA-free diets having graded reductions of α-linolenic acid (α-LNA). Compared with control diet (4.6% α-LNA), plasma DHA fell significantly at 1.7% dietary α-LNA while brain DHA remained unchanged down to 0.8% α-LNA, when plasma and brain docosapentaenoic acid (DPAn-6) were increased and DHA-selective iPLA(2) and COX-1 activities were downregulated. Brain AA was unchanged by deprivation, but AA selective-cPLA(2), sPLA(2) and COX-2 activities were increased at or below 0.8% dietary α-LNA, possibly in response to elevated brain DPAn-6. In summary, homeostatic mechanisms appear to maintain a control brain DHA concentration down to 0.8% dietary DHA despite reduced plasma DHA, when DPAn-6 replaces DHA. At extreme deprivation, decreased brain iPLA(2) and COX-1 activities may reduce brain DHA loss.

Retailoring docosahexaenoic acid-containing phospholipid species during impaired neurogenesis following omega-3 alpha-linolenic acid deprivation.

Diminished levels of docosahexaenoic acid (22:6n-3), the major fatty acid (FA) synthesized from alpha-linolenic acid (18:3n-3), have been implicated in functional impairment in the developing and adult brain. We have now examined the changes in phospholipid (PL) molecular species in the developing postnatal cortex, a region recently shown to be affected by a robust aberration in neuronal cell migration, after maternal diet alpha-linolenic acid deprivation (Yavin et al. (2009)Neuroscience162(4),1011). The frontal cortex PL composition of 1- to 4-week-old rats was analyzed by gas chromatography and electrospray ionization/tandem mass spectrometry. Changes in the cortical PL molecular species profile by dietary means appear very specific as 22:6n-3 was exclusively substituted by docosapentaenoic acid (22:5n-6). However, molecular species were conserved with respect to the combination of specific polar head groups (i.e. ethanolamine and serine) in sn-3 and defined saturated/mono-unsaturated FA in sn-1 position even when the sn-2 FA moiety underwent diet-induced changes. Our results suggest that substitution of docosahexaenoic acid by docosapentaenoic acid is tightly regulated presumably to maintain a proper biophysical characteristic of membrane PL molecular species. The importance of this conservation may underscore the possible biochemical consequences of this substitution in regulating certain functions in the developing brain.

Developmental effects of dietary n-3 fatty acids on activity and response to novelty.

Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing alpha-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in alpha-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects.

Gender affects liver desaturase expression in a rat model of n-3 fatty acid repletion.

Dietary n-3 polyunsaturated fatty acids (PUFA) are major components of cell membranes and have beneficial effects on human health. Docosahexaenoic acid (DHA; 22:6n-3) is the most biologically important n-3 PUFA and can be synthesized from its dietary essential precursor, alpha-linolenic acid (ALA; 18:3n-3). Gender differences in the efficiency of DHA bioconversion have been reported, but underlying molecular mechanisms are unknown. We compared the capacity for DHA synthesis from ALA and the expression of related enzymes in the liver and cerebral cortex between male and female rats. Wistar rats, born with a low-DHA status, were supplied with a suboptimal amount of ALA from weaning to 8 weeks of age. Fatty acid composition was determined by gas chromatography, the mRNA expression of different genes involved in PUFA metabolism was determined by RT-PCR (low-density array) and the expression of proteins was determined by Western blot analysis. At 8 weeks, DHA content was higher (+20 to +40%) in each phospholipid class of female livers compared to male livers. The "Delta4," Delta5 and Delta6 desaturation indexes were 1.2-3 times higher in females than in males. The mRNA expression of Delta5- and Delta6-desaturase genes was 3.8 and 2.5 times greater, respectively, and the Delta5-desaturase protein was higher in female livers (+50%). No gender difference was observed in the cerebral cortex. We conclude that female rats replete their DHA status more readily than males, probably due to a higher expression of liver desaturases. Our results support the hypothesis on hormonal regulation of PUFA metabolism, which should be taken into account for specific nutritional recommendations.

Delayed cell migration in the developing rat brain following maternal omega 3 alpha linolenic acid dietary deficiency.

Diminished levels of docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid (FA) synthesized from alpha linolenic acid (ALA, 18:3n-3), have been implicated in changes in neurotransmitter production, ion channel disruption and impairments of a variety of cognitive, behavioral and motor functions in the perinatal and adult mammal. Neuronal migration in the cortex and hippocampus of newborn and postnatal rats after ALA-deficiency, beginning on the 2nd day after conception and continuing for three weeks, was investigated. A marked decrease in the migration of bromodeoxyuridine((+))/neuronal nuclei((+))/neurofilament((+)) and glia fibrillary acidic protein((-)) neuronal cells to the dense cortical plate was accompanied by a corresponding abundance of non-migrating cells in several regions such as cortical layers IV-VI, corpus callosum and the sub-ventricular zone of ALA-deficient newborns. Similarly, a delayed migration of cells to CA1 and dentate gyrus areas was noticed while most cells were retained in the subicular area adjacent to the hippocampus. The reversibility of delay in migration in the hippocampus and cortex, after one and two weeks respectively, may be attributed to a temporary reelin disorganization or partial deficiency. Transient obstruction of neuronal cell migration may have long-lasting consequences on the organization of neuronal assemblies, on the connection between neurons (lateral connections) and acquisition of function in the adult brain.

Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo (1)H-MRS study.

To investigate the effects of omega-3 fatty acid deficiency on phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by in vivo proton magnetic resonance spectroscopy ((1)H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning alpha-linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a (1)H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D(1) receptors. Postmortem PFC fatty acid composition was determined by gas chromatography. Relative to controls, PFC DHA composition was significantly reduced in adult postweaning (-27%) and perinatal (-65%) ALA-deficiency groups. Basal PFC mI concentrations were significantly reduced in the perinatal deficiency group (-21%, P = 0.001), but not in the postweaning deficiency group (-1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly increased mI concentrations only in the perinatal deficiency group (+16%, P = 0.02). These data demonstrate that perinatal deficits in cortical DHA accrual significantly and selectively reduce mI concentrations and augment receptor-generated mI synthesis.

Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats.

Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in the etiologies of non-puerperal and postpartum depression. With the aim of determining neurobiological sequelae of decreased brain DHA content, this study examined the effects of a loss of brain DHA content and concurrent reproductive status in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 23-26% lower than virgin and parous rats fed a control diet containing adequate alpha-linolenic acid. Parous dams were tested/euthanized at weaning (postnatal day 20) of the second litter; virgin females, during diestrus. Decreased brain DHA was associated with decreased hippocampal BDNF gene expression and increased relative corticosterone response to an intense stressor, regardless of reproductive status. In virgin females with decreased brain DHA, serotonin content and turnover in frontal cortex were decreased compared to virgin females with normal brain DHA. In parous dams with decreased brain DHA, the density of 5-HT(1A) receptors in the hippocampus was increased, corticosterone response to an intense stressor was increased, and the latency to immobility in the forced swim test was decreased compared to parous dams with normal DHA. These findings demonstrate neurobiological alterations attributable to decreased brain DHA or an interaction of parous status and brain DHA level. Furthermore, the data are consistent with findings in depressed humans, and thus support a role for DHA as a factor in the etiologies of depressive illnesses, particularly postpartum depression.

Coping strategies and nutritional health in rural Niger: recommendations for consumption of wild plant foods in the Sahel.

People who live in food and water deficit regions of Sahelien West Africa employ various coping strategies as they attempt to meet their food and water needs. In this paper we discuss various coping strategies employed by rural Nigeriens living in the Tanout and Mirriya administrative regions of central Niger. In rural Niger people often harvest or buy wild plant foods to eat. Laboratory studies of the nutritional content of these plants indicate that there are benefits to eating wild plant foods. In this study we summarize the results of field research conducted during the summer of 2002 on the use of wild plant foods in three regions of rural central Niger. Comparing local use of various wild plant foods with major nutrition-related health problems including protein deficiency, essential fatty acid deficiency, iron deficiency and iron deficiency anemia, calcium deficiency rickets, and zinc deficiency, suggests potential recommendations for consumption of these plants. However, further research on the bioavailability of these nutrients is needed to confirm the potential benefits of these plants.

[Alpha-linolenic acid, cardiovascular disease and sudden death]. / Alfalinolensyre, kardiovaskulaer sykdom og plutselig død.

BACKGROUND: Several animal experiments have documented that omega-3 fatty acid alpha-linolenic acid (ALA) (C 18:3, n-3) from vegetable oils has beneficial electrophysiological and antiarrhythmic effects. This may explain the protective effect of ALA against cardiovascular diseases and sudden death. MATERIALS AND METHODS: We have continuously and systematically collected and evaluated relevant literature (observational and secondary prophylactic studies) and here present an overview of the effects of ALA on cardiovascular diseases and sudden death. RESULTS: Several observational studies in healthy individuals and in patients with coronary heart disease have indicated that a diet rich in ALA reduces coronary death and the risk for sudden death. A cross-sectional study has shown a beneficial effect of ALA on the progression of coronary atherosclerosis. Three secondary studies have also indicated beneficial effects of ALA on several cardiovascular end-points. Diet studies do have limitations, and the secondary prophylactic studies have not given a definite answer to whether ALA possesses beneficial cardiovascular effects. INTERPRETATION: On the whole, the observational and secondary prophylactic studies indicate that ALA may have cardioprotective effects in healthy individuals and in patients with coronary heart disease. For those who seldom eat fish and only take small amounts of fish oils, a diet rich on ALA may be an alternative.

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion.

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

Effects of an n-3-deficient diet on brain, retina, and liver fatty acyl composition in artificially reared rats.

Rat pups born to dams fed a diet with 3.1% of total fatty acids as alpha-linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model.

Biochemical crypsis in the avoidance of natural enemies by an insect herbivore.

Plant-herbivore interactions provide well studied examples of coevolution, but little is known about how such interactions are influenced by the third trophic level. Here we show that larvae of the specialized lepidopteran herbivore Heliothis subflexa reduce their vulnerability to natural enemies through adaptation to a remarkable and previously unknown feature of their host plant, Physalis angulata: The fruits of this plant lack linolenic acid (LA), which is required for the development of most insects. By overcoming this nutritional deficiency, H. subflexa larvae achieve numerous advantages. First, they gain near-exclusive access to a food resource: we demonstrate that closely related Heliothis virescens larvae cannot develop on P. angulata fruit unless the fruit are treated with LA. Second, they reduce their vulnerability to enemies: LA is a key component of volicitin, an elicitor of plant-volatile-signaling defenses. We demonstrate that volicitin is absent in the oral secretions of fruit-feeding caterpillars, that the volatile profiles of plants induced by fruit feeding differ from those induced by leaf feeding or by feeding on LA-treated fruit, and that the former are far less attractive to female Cardiochiles nigriceps parasitoids. Finally, they render themselves nutritionally unsuitable as hosts for enemies that require LA for their own development: we show that C. nigriceps larvae fail to develop within the bodies of fruit-feeding caterpillars but do develop in caterpillars feeding on LA-treated fruit. Thus, H. subflexa larvae not only overcome a serious dietary deficiency but also reduce their vulnerability to natural enemies through a form of "biochemical crypsis."

Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat.

We explored the effects of chronic alpha-linolenic acid dietary deficiency on serotoninergic neurotransmission. In vivo synaptic serotonin (5-HT) levels were studied in basal and pharmacologically stimulated conditions using intracerebral microdialysis in the hippocampus of awake 2-month-old rats. We also studied the effects of reversion of the deficient diet on fatty acid composition and serotoninergic neurotransmission. A balanced (control) diet was supplied to deficient rats at different stages of development, i.e. from birth, 7, 14 or 21 days of age. We demonstrated that chronic n-3 polyunsaturated fatty acid dietary deficiency induced changes in the synaptic levels of 5-HT both in basal conditions and after pharmacological stimulation with fenfluramine. Higher levels of basal 5-HT release and lower levels of 5-HT-stimulated release were found in deficient than in control rats. These neurochemical modifications were reversed by supply of the balanced diet provided at birth or during the first 2 weeks of life through the maternal milk, whereas they persisted if the balanced diet was given from weaning (at 3 weeks of age). This suggests that provision of essential fatty acids is durably able to affect brain function and that this is related to the developmental stage during which the deficiency occurs.