Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet.

SCOPE: Perinatal maternal moderately high-fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n-3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning. METHODS AND RESULTS: Female Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high-fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics. CONCLUSIONS: Gestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long-term outcomes.

Quality of Life and a Surveillant Endocannabinoid System.

The endocannabinoid system (ECS) is an important brain modulatory network. ECS regulates brain homeostasis throughout development, from progenitor fate decision to neuro- and gliogenesis, synaptogenesis, brain plasticity and circuit repair, up to learning, memory, fear, protection, and death. It is a major player in the hypothalamic-peripheral system-adipose tissue in the regulation of food intake, energy storage, nutritional status, and adipose tissue mass, consequently affecting obesity. Loss of ECS control might affect mood disorders (anxiety, hyperactivity, psychosis, and depression), lead to drug abuse, and impact neurodegenerative (Alzheimer's, Parkinson, Huntington, Multiple, and Amyotrophic Lateral Sclerosis) and neurodevelopmental (autism spectrum) disorders. Practice of regular physical and/or mind-body mindfulness and meditative activities have been shown to modulate endocannabinoid (eCB) levels, in addition to other players as brain-derived neurotrophic factor (BDNF). ECS is involved in pain, inflammation, metabolic and cardiovascular dysfunctions, general immune responses (asthma, allergy, and arthritis) and tumor expansion, both/either in the brain and/or in the periphery. The reason for such a vast impact is the fact that arachidonic acid, a precursor of eCBs, is present in every membrane cell of the body and on demand eCBs synthesis is regulated by electrical activity and calcium shifts. Novel lipid (lipoxins and resolvins) or peptide (hemopressin) players of the ECS also operate as regulators of physiological allostasis. Indeed, the presence of cannabinoid receptors in intracellular organelles as mitochondria or lysosomes, or in nuclear targets as PPARγ might impact energy consumption, metabolism and cell death. To live a better life implies in a vigilant ECS, through healthy diet selection (based on a balanced omega-3 and -6 polyunsaturated fatty acids), weekly exercises and meditation therapy, all of which regulating eCBs levels, surrounded by a constructive social network. Cannabidiol, a diet supplement has been a major player with anti-inflammatory, anxiolytic, antidepressant, and antioxidant activities. Cognitive challenges and emotional intelligence might strengthen the ECS, which is built on a variety of synapses that modify human behavior. As therapeutically concerned, the ECS is essential for maintaining homeostasis and cannabinoids are promising tools to control innumerous targets.

Maternal high-fat diet up-regulates type-1 cannabinoid receptor with estrogen signaling changes in a sex- and depot- specific manner in white adipose tissue of adult rat offspring.

PURPOSE: Obesity and high-fat (HF) diet are associated with over activation of the endocannabinoid system (ECS). We have demonstrated that maternal HF diet induces early obesity and modulates cannabinoid signaling in visceral (VIS) and subcutaneous (SUB) white adipose tissue (WAT) in weanling rat offspring. We hypothesized that perinatal maternal HF diet would program the expression of ECS in adipose tissue in a long-term way in parallel to alterations in epigenetic markers and sex hormone signaling. METHODS: Progenitor female rats received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) for 8 weeks before mating, gestation, and lactation. All pups were weaned to C diet and they were euthanized at 180 days old. RESULTS: Maternal HF diet induced overweight and increased SUB WAT mass of male and female adult offspring. Maternal HF diet induced hypertrophy of VIS and SUB adipocytes only in female offspring associated with increased type 1 cannabinoid receptor protein (CB1) and mRNA (Cnr1) levels. These changes were associated with increased estrogen receptor α binding to Cnr1 promoter in SUB WAT of adult female offspring, which may contribute to higher expression of Cnr1. CONCLUSION: Increased CB1 signaling in adipose tissue might contribute to higher adiposity programmed by maternal HF diet because endocannabinoids stimulate the accumulation of fat in the adipose tissue. Our findings provide molecular insights into sex-specific targets for anti-obesity therapies based on the endocannabinoid system.

Maternal high-fat diet consumption induces sex-dependent alterations of the endocannabinoid system and redox homeostasis in liver of adult rat offspring.

Maternal diet plays a critical role in health development. Perinatal overnutrition induces metabolic dysfunctions and obesity in the offspring. Obesity is associated with endocannabinoid system (ECS) over activation and oxidative stress. Liver ECS activation induces hepatic steatosis, inflammation and fibrosis while the antagonism of cannabinoid receptors ameliorates these alterations. Here, we investigated the effect of perinatal maternal high-fat diet (HF, 29% of calories as fat) on the ECS and antioxidant system in liver of male and female adult rat offspring (180 days old). Maternal HF diet increased hepatic cannabinoid receptors, ECS metabolizing enzymes and triglyceride content, with male offspring more affected. ECS changes are likely independent of estradiol serum levels but associated with increased hepatic content of estrogen receptor, which can stimulate the expression of ECS components. Differently, maternal HF diet decreased the activity of the antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase, and increased oxidative stress markers in both sexes. Alterations in the redox homeostasis were associated with mitochondria damage but not with liver fibrosis. Our data suggest that maternal HF diet induces ECS over activation in adulthood, and that male offspring are at higher risk to develop liver disease compared with female rats.

The phytoecdysteroid ß-ecdysone is genotoxic in Rodent Bone Marrow Micronuclei and Allium cepa L. Assays.

ETHNAOPHARMACOLOGIAL RELEVANCE: In South America, the ß-ecdysone ecdysteroid has been found in species of the genus Pfaffia Mart. Due to the similar morphology of its roots to the Panax ginseng C. A. Mey. (Korean ginseng), some species of this genus has been known as Brazilian ginseng and have been used as tonic and aphrodisiac, as well as for the treatment of diabetes and rheumatism. AIM OF THE STUDY: Here we report a cytogenotoxic evaluation of ß-ecdysone (a natural ecdysteroid found in plants) in Rodent Bone Marrow Micronuclei and Allium cepa Assays. MATERIALS AND METHODS: Three ß-ecdysone (pure) concentrations (based in human therapeutic dosage) were used in the Micronucleus Assay. The animals were treated during two consecutive days. Micronucleated cells were counted in 2000 polychromatic erythrocytes per animal. For A. cepa L. Assay, one ß-ecdysone concentration was analyzed. The onions bulbs were exposed for 24h. RESULTS: The Micronucleus Assay showed genotoxic effects for all treatments, expressed by an increase of micronucleated cells. In A. cepa L. Assay, cell abnormalities associated to the malfunction/non-formation of mitotic spindle (aneugenic effect) and chromosomal bridges (clastogenic effect) were observed. CONCLUSIONS: The results indicate a cytogenotoxic activity of ß-ecdysone. Therefore, the popular use of Pfaffia and others species containing ß-ecdysone should be considered with caution.

Cis-9, trans-11 and trans-10, cis-12 CLA mixture does not change body composition, induces insulin resistance and increases serum HDL cholesterol level in rats.

Synthetic supplements of conjugated linoleic acid (CLA) containing 50:50 mixture of cis-9, trans-11 and trans-10, cis-12 CLA isomers have been commercialized in some places for reducing body fat. However the safety of this CLA mixture is controversial and in some countries the CLA usage as food supplement is not authorized. Changes in insulinemic control and serum lipids profile are potential negative effects related to consumption of CLA mixture. The present study aimed to evaluate the effects of a diet containing mixture of cis-9, trans-11 and trans-10, cis-12 CLA on prevention of obesity risk as well as on potential side effects such as insulin resistance and dyslipidemia in Wistar rats. Thirty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: Normolipidic Control (NC), diet containing 4.0% soybean oil (SO); High Fat-Control (HF-C), diet containing 24.0% SO; High Fat-synthetic CLA (HF-CLA), diet containing 1.5% of an isomeric CLA mixture (Luta-CLA 60) and 22.5% SO. Luta-CLA 60 (BASF) contained nearly 60% of CLA (cis-9, trans-11 and trans-10, cis-12 CLA at 50:50 ratio). The HF-CLA diet contained 0.3% of each CLA isomer. HF-CLA diet had no effect on dietary intake and body composition. HF-CLA-fed rats had lower levels of PPARγ protein in retroperitoneal adipose tissue, hyperinsulinemia compared to HF-C-fed rats, hyperglycemia compared to NC-fed rats while no differences in glycemia were observed between NC and HF-C groups, increased HOMA index and higher levels of serum HDL cholesterol. Thus, feeding rats with a high fat diet containing equal parts of cis-9, trans-11 and trans-10, cis-12 CLA isomers had no effect on body composition and induced insulin resistance. Despite HF-CLA-fed rats had increased serum HDL cholesterol levels, caution should be taken before synthetic supplements containing cis-9, trans-11 and trans-10, cis-12 CLA are recommended as a nutritional strategy for weight management.

Butter naturally enriched in cis-9, trans-11 CLA prevents hyperinsulinemia and increases both serum HDL cholesterol and triacylglycerol levels in rats.

BACKGROUND: Evidence from in vitro and animal studies indicates that conjugated linoleic acid (CLA) possesses anti-diabetic properties, which appear to be attributed to cis-9, trans-11 CLA, the major CLA isomer in ruminant fat. However, there is a shortage of studies addressing CLA from natural source. The present study aimed to evaluate the effects of butter naturally enriched in cis-9, trans-11 CLA on parameters related to glucose tolerance, insulin sensitivity and dyslipidemia in rats. METHODS: Forty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: 1) Normal fat-Soybean oil (NF-So): diet containing 4.0% soybean oil (SO); 2) High Fat-Control Butter (HF-Cb): diet containing 21.7% control butter and 2.3% SO; 3) High Fat-CLA enriched Butter (HF-CLAb): diet containing 21.7% cis-9, trans-11 CLA-enriched butter and 2.3% SO; and 4) High fat-Soybean oil (HF-So): diet containing 24.0% SO. HF-Cb and HF-CLAb diets contained 0.075% and 0.235% of cis-9, trans-11 CLA, respectively. RESULTS: HF-CLAb-fed rats had lower serum insulin levels at fasting than those fed with the HF-Cb diet, while the PPARγ protein levels in adipose tissue was increased in HF-CLAb-fed rats compared to HF-Cb-fed rats. Furthermore, R-QUICK was lower in HF-Cb than in NF-So group, while no differences in R-QUICK were observed among NF-So, HF-CLAb and HF-So groups. Serum HDL cholesterol levels were higher in HF-CLAb-fed rats than in those fed NF-So, HF-Cb and HF-So diets, as well as higher in NF-So-fed rats than in HF-Cb and HF-So-fed rats. HF-CLAb, HF-Cb and HF-So diets reduced serum LDL cholesterol levels when compared to NF-So, whereas serum triacylglycerol levels were increased in HF-CLAb. CONCLUSION: Feeding rats on a high-fat diet containing butter naturally enriched in cis-9, trans-11 CLA prevented hyperinsulinemia and increased HDL cholesterol, which could be associated with higher levels of cis-9, trans-11 CLA, vaccenic acid, oleic acid and lower levels of short and medium-chain saturated fatty acids from butter naturally modified compared to control butter. On the other hand CLA-enriched butter also increased serum triacylglycerol levels, which could be associated with concomitant increases in the content of trans-9 and trans-10 C18:1 isomers in the CLA-enriched butter.