Trans-fat supplementation over two generations of rats exacerbates behavioral and biochemical damages in a model of mania: Co-treatment with lithium.

AIMS: We investigated whether trans-fat supplemented over two generations of rats could alter neuronal membranes and influence mania-like behaviors, as well as the effects of lithium (Li). MAIN METHODS: Two generations of female rats were supplemented with soybean oil (SO-C, rich in n-6 fatty acids - FA) or hydrogenated vegetable fat (HVF, rich in trans-fatty acids - TFA). Male rats born from the 1st and 2nd generations were maintained in the same supplementation until adulthood, when they were exposed to an amphetamine (AMPH)-induced model of mania and co-treated with Li or not. KEY FINDINGS: AMPH increased locomotion of both generations and this influence was higher in the HVF than in the SO-C group. Conversely, AMPH increased long-term memory in SO-C group of the 2nd generation. HVF supplementation allowed hippocampal TFA incorporation in rats of both generations (0.1 and 0.2%, respectively). Oxidative parameters indicated higher levels of protein carbonyl (PC) in the HVF group with no changes in catalase (CAT) activity in the 1st generation. In the 2nd generation, AMPH increased PC levels of both experimental groups, whereas CAT activity was lower per se in the HVF group only. The co-treatment with Li leveled out all behavioral parameters, PC levels and CAT activity indicating a significant neuroprotective role. SIGNIFICANCE: These findings suggest that chronic HVF consumption allows a rising incorporation of TFA in the brain, which may be reflected on the neuropsychiatric conditions related to mania, whereas the effects of Li are not modified in the course of this harmful dietary habit.

Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors.

Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD).

Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin.

We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer.

Trans fat supplementation increases UV-radiation-induced oxidative damage on skin of mice.

We evaluated the influence of fish oil (FO, rich in n-3 FA), soybean oil (SO, rich in n-6 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) on the oxidative status and viability of skin cells of mice exposed to ultraviolet radiation (UVR). Mice were supplemented with FO, SO or HVF for three months and exposed to UVR (2.72 mJ/cm(2)) for 2 days. One day after the last UVR session, the FO group showed higher levels of n-3 fatty acids (FA), while the HVF showed higher incorporation of trans FA (TFA) in dorsal skin. UVR increased lipid peroxidation and protein carbonyl levels of the HVF and to a lesser extent of the control and SO groups. Although all irradiated groups showed increased skin thickness, this increase was slighter in FO mice. UVR exposure reduced skin cell viability of the control, SO and HVF groups, while FO prevented this. Catalase activity was reduced independently of the supplementation and SOD level was increased in C and FO groups after UVR exposure; FO prevented the UVR-induced increase in glutathione levels, which was observed in skin of the control, SO and HVF mice. Our results showed the beneficial effects of FO supplementation, as well as the harmful effects of trans FA, whose intensity can increase vulnerability to skin diseases.

Influence of lifelong dietary fats on the brain fatty acids and amphetamine-induced behavioral responses in adult rat.

The influence of dietary fatty acids (FA) on mania-like behavior and brain oxidative damage were evaluated in rats. First generation of rats born and maintained under supplementation with soybean-oil (SO), fish-oil (FO) or hydrogenated-vegetable-fat (HVF), which are rich in n-6, n-3 and trans (TFA) FA, respectively, until adulthood, were exposed to an amphetamine (AMPH)-induced mania animal model to behavioral and biochemical evaluations. While AMPH caused hyperlocomotion in HVF and, to a less extent, in SO- and FO-groups, a better memory performance was observed in FO group. Among vehicle-groups, HVF increased reactive species (RS) generation and protein-carbonyl (PC) levels in cortex; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. Among AMPH-treated animals, HVF exacerbated RS generation in all evaluated brain areas and increased PC levels in cortex and striatum; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. FO was related to higher percentage of polyunsaturated fatty acids (PUFA) and docosahexaenoic acid (DHA) in cortex and striatum, while HVF was associated to higher incorporation of TFA in cortex, hippocampus and striatum, besides increased n-6/n-3 FA ratio in striatum. While a continuous exposure to TFA may intensify oxidative events in brain, a prolonged FO consumption may prevent mania-like-behavior; enhance memory besides decreasing brain oxidative markers. A substantial inclusion of processed foods, instead of foods rich in omega-3, in the long term is able to influence the functionality of brain structures related to behavioral disturbances and weaker neuroprotection, whose impact should be considered by food safety authorities and psychiatry experts.

Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane-bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat.

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.