Fetal programming by androgen excess impairs liver lipid content and PPARg expression in adult rats.

It is known that prenatal hyperandrogenization induces alterations since early stages of life, contributing to the development of polycystic ovary syndrome affecting the reproductive axis and the metabolic status, thus promoting others associated disorders, such as dyslipidemia, insulin resistance, liver dysfunction, and even steatosis. In this study, we aimed to evaluate the effect of fetal programming by androgen excess on the hepatic lipid content and metabolic mediators at adult life. Pregnant rats were hyperandrogenized with daily subcutaneous injections of 1 mg of free testosterone from days 16 to 19 of pregnancy. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory phenotype (PHiov) and anovulatory phenotype (PHanov), with different metabolic and endocrine features. We evaluated the liver lipid content and the main aspect of the balance between fatty acid (FA) synthesis and oxidation. We investigated the status of the peroxisomal proliferator-activated receptors (PPARs) alpha and gamma, which act as lipid mediators, and the adipokine chemerin, one marker of liver alterations. We found that prenatal hyperandrogenization altered the liver lipid profile with increased FAs levels in the PHanov phenotype and decreased cholesterol content in the PHiov phenotype. FA metabolism was also disturbed, including decreased mRNA and protein PPARgamma levels and impaired gene expression of the main enzymes involved in lipid metabolism. Moreover, we found low chemerin protein levels in both PH phenotypes. In conclusion, these data suggest that prenatal hyperandrogenization exerts a negative effect on the liver and alters lipid content and metabolic mediators' expression at adult age.

Decreased body-fat accumulation and increased vasorelaxation to glyceryl trinitrate in middle-aged male rats following six-weeks consumption of coconut milk protein

Abstract We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats

Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

Choline supplementation for Hisex Brown and Hisex White laying hens. 2. Liver lipid deposition and plasma lipids levels. / Suplementação de colina para poedeiras comerciais Hisex Brown e hisex White. 2. Deposição de gordura hepática e níveis de lipídeos plasmáticos

64 sixty four week-old Hisex Brown and 64 sixty three week-old Hisex White were fed 4 experimental diets containing 500, 1000, 1500 and 2000 mg of choline/kg. the methionine level was 0.253% for all the experimental diets, equivalent to 80% of the National Research Council requirements. Although the liver weight (g) values were significantly higher for the Hisex Brown strain, liver weight (% BW), liver lipid, plasma estradiol, total plama lipids, plasma triglycerides and plasma total cholesterol did not differ significantly between strains. Plasma GOT and plasma HDL-cholesterol were significantly hogher for the Hisex Brown birds. The choline supplementation at the levels of 1500 and 2000 mg/kg determined a significant reduction of the liver lipid deposition. It was found a significant negative correlation between dietetic levels of choline and total plasma lipids (r = -0,287).  

64 galinhas da linhagem Hisex Brown e 64 da linhagem Hisex White, apresentando respectivamente, 63 e 64 semanas de idade, foram alimentadas com rações à base de milho e farelo de soja contendo suplementação de 500, 1000, 1500 e 2000 mg de colina por quilo e nível constante de 0,253% de metionina para todas as dietas experimentais, correspondendo a 80% das necessidades estabelecidas pelo National Research Council. Embora as galinhas Hisex Brown tivessem apresentado peso do fígado (g) significativamente maior que as Hisex White, não foram consignadas diferenças entre as linhagens estudadas no relativo à gordura hepática, níveis plasmáticos de estradiol, lipídeos totais, triglicérides e colesterol total. Os valores de TGO e colesterol HDL no plasma, mostraram-se significativamente mãos elevados nas aves da linhagem Hisex Brown. A adição de colina à dieta, em níveis de 1500 e 2000 mg/kg, determinou redução significativa entre os valores de colina suplementar na dieta e dos lipídeos totais no plasma (r = - 0,287).

Choline supplementation for Hisex Brown and Hisex White laying hens. 2. Liver lipid deposition and plasma lipids levels / Suplementação de colina para poedeiras comerciais Hisex Brown e hisex White. 2. Deposição de gordura hepática e níveis de lipídeos plasmáticos

64 sixty four week-old Hisex Brown and 64 sixty three week-old Hisex White were fed 4 experimental diets containing 500, 1000, 1500 and 2000 mg of choline/kg. the methionine level was 0.253% for all the experimental diets, equivalent to 80% of the National Research Council requirements. Although the liver weight (g) values were significantly higher for the Hisex Brown strain, liver weight (% BW), liver lipid, plasma estradiol, total plama lipids, plasma triglycerides and plasma total cholesterol did not differ significantly between strains. Plasma GOT and plasma HDL-cholesterol were significantly hogher for the Hisex Brown birds. The choline supplementation at the levels of 1500 and 2000 mg/kg determined a significant reduction of the liver lipid deposition. It was found a significant negative correlation between dietetic levels of choline and total plasma lipids (r = -0,287).

64 galinhas da linhagem Hisex Brown e 64 da linhagem Hisex White, apresentando respectivamente, 63 e 64 semanas de idade, foram alimentadas com rações à base de milho e farelo de soja contendo suplementação de 500, 1000, 1500 e 2000 mg de colina por quilo e nível constante de 0,253% de metionina para todas as dietas experimentais, correspondendo a 80% das necessidades estabelecidas pelo National Research Council. Embora as galinhas Hisex Brown tivessem apresentado peso do fígado (g) significativamente maior que as Hisex White, não foram consignadas diferenças entre as linhagens estudadas no relativo à gordura hepática, níveis plasmáticos de estradiol, lipídeos totais, triglicérides e colesterol total. Os valores de TGO e colesterol HDL no plasma, mostraram-se significativamente mãos elevados nas aves da linhagem Hisex Brown. A adição de colina à dieta, em níveis de 1500 e 2000 mg/kg, determinou redução significativa entre os valores de colina suplementar na dieta e dos lipídeos totais no plasma (r = - 0,287).