Hepatic resistance to cold ferroptosis in a mammalian hibernator Syrian hamster depends on effective storage of diet-derived α-tocopherol

Mammalian hibernators endure severe and prolonged hypothermia that is lethal to non-hibernators, including humans and mice. The mechanisms responsible for the cold resistance remain poorly understood. Here, we found that hepatocytes from a mammalian hibernator, the Syrian hamster, exhibited remarkable resistance to prolonged cold culture, whereas murine hepatocytes underwent cold-induced cell death that fulfills the hallmarks of ferroptosis such as necrotic morphology, lipid peroxidation and prevention by an iron chelator. Unexpectedly, hepatocytes from Syrian hamsters exerted resistance to cold- and drug-induced ferroptosis in a diet-dependent manner, with the aid of their superior ability to retain dietary α-tocopherol (αT), a vitamin E analog, in the liver and blood compared with those of mice. The liver phospholipid composition is less susceptible to peroxidation in Syrian hamsters than in mice. Altogether, the cold resistance of the hibernator’s liver is established by the ability to utilize αT effectively to prevent lipid peroxidation and ferroptosis.

Degradation of Phospholipids by N, N-Dimethylformamide Induced Liver Toxicity in Male Wistar Rats

Dimethylformamide (DMF) is an industrially used solvent, prioritized by the National Toxicology Program as a potent hepatotoxic compound. The effect of DMF on liver is well documented; however its impact on hepatic phospholipids remains enigmatic. Hence, to understand the phospholipid metabolism we have developed an animal model for DMF induced hepatotoxicity. In the present study, DMF (0.5, 1.0, 1.5 g/kg body wt) was given intraperitoneally to male wistar rats and terminated after 24 and 48 h. DMF with a concentration of 1.5 g/kg body wt shows maximum toxic effect. Dosages higher than 1.5 g/kg body wt showed lethal effect, hence in this study, 1.5 g/kg body wt was used as maximum concentration. Induction of hepatotoxicity by DMF was confirmed by liver marker enzymes. DMF impairs the liver phospholipid metabolism. DMF decreased the individual phospholipid levels by altering the fatty acid composition. There was an increase in unsaturated fatty acids with a concomitant decrease in saturated fatty acid. These changes in the fatty acid may directly or indirectly affect the membrane structure and fluidity. Understanding the mechanism by which DMF induced hepatotoxicity and alteration in phospholipid metabolism is a worthwhile pursuit.

Changes in lipid profile of rats fed with Agaricus bisporus (white button) mushroom

Purpose White button (Agaricus bisporus) mushroom (WBM) is a good source of fiber, protein and unsaturated fatty acids and is considered an effective food for the treatment of hyperlipidemia. Design/methodology/approach Male Wistar strain rats (28) were divided into four groups, two control and two experimental, which were fed a semi-synthetic diet containing 1 per cent cholesterol and supplemented with 5 and 10 per cent dried mushroom for a period of 42 days. At the end of the experiment, the rats were anesthetized and blood samples were taken. The serum and liver were analyzed for total lipids, triglycerides and phospholipids. Findings Serum total lipid and triglyceride levels were reduced significantly in rats fed on 5 and 10 per cent WBM. However, serum phospholipid levels were decreased only in rats fed on 10 per cent WBM. The deposition of total lipids and triglycerides in liver decreased significantly in the experimental rats. However, no significant differences were observed in liver phospholipid levels in any experimental group of rats. Originality/value Hyperlipidemia is one of the leading medical problems nowadays, and it represents a major concern because of the associated death rates occurring in different communities. The study results indicate that this problem can be reduced through the consumption of A. bisporus mushrooms.

Effects of Aronia melanocarpa juice on plasma and liver phospholipid fatty acid composition in Wistar rats

A nutritional placebo-controlled study was performed in Wistar rats in order to investigate the effects of 5-weeks aronia juice consumption towards fatty acid (FA) composition of phospholipids in the plasma and liver, as well as plasma glucose (Glu) and cholesterol levels. The animals were divided into 3 groups of 8 animals each, and randomized to receive either the full polyphenol dose of Aronia melanocarpa juice (AMJ), 4 times less polyphenol dose (¼-AMJ) or polyphenol-lacking placebo beverage (PLB). Each group of 8 male adult Wistar rats received the liquid ad libitum. AMJ decreased the levels of low-density lipoprotein (LDL) (P < 0.05) vs. PLB. AMJ increased dihomo-γ-linoleic acid (DGLA, 20:3n-6) (P < 0.05) and decreased arachidonic acid content (AA, 20:4n-6) (P < 0.05) vs. PLB in liver phospholipids. AMJ significantly increased monounsaturated fatty acids (MUFA) levels both in the liver (P < 0.05) and plasma (P < 0.05). Both aronia juice doses elevated the levels of beneficial n-3 polyunsaturated fatty acids (PUFA) in the plasma and liver. There was a dose-dependent, significant increase (P < 0.001) in cis-vaccenic acid (VA, 18:1n-7) in phospholipids in the plasma and liver. Our results indicate favorable effects of aronia juice intake on lipid parameters in Wistar rats. These findings suggest the potential of aronia dietary intake in cardiometabolic diseases primary prevention strategies in the human population.

Methionine deficiency does not increase polyamine turnover through depletion of hepatic S-adenosylmethionine in juvenile Atlantic salmon

During the last few decades, plant protein ingredients such as soya proteins have replaced fishmeal in the diets of aquacultured species. This may affect the requirement and metabolism of methionine as soya contains less methionine compared with fishmeal. To assess whether methionine limitation affects decarboxylated S-adenosylmethionine availability and polyamine status, in the present study, juvenile Atlantic salmon were fed a methionine-deficient plant protein-based diet or the same diet supplemented with dl-methionine for 8 weeks. The test diets were compared with a fishmeal-based control diet to assess their effects on the growth performance of fish. Methionine limitation reduced growth and protein accretion, but when fish were fed the dl-methionine-supplemented diet their growth and protein accretion equalled those of fish fed the fishmeal-based control diet. Methionine limitation reduced free methionine concentrations in the plasma and muscle, while those in the liver were not affected. S-adenosylmethionine (SAM) concentrations were higher in the liver of fish fed the methionine-deficient diet, while S-adenosylhomocysteine concentrations were not affected. Putrescine concentrations were higher and spermine concentrations were lower in the liver of fish fed the methionine-deficient diet, while the gene expression of SAM decarboxylase (SAMdc) and the rate-limiting enzyme of polyamine synthesis ornithine decarboxylase (ODC) was not affected. Polyamine turnover, as assessed by spermine/spermidine acetyltransferase (SSAT) abundance, activity and gene expression, was not affected by treatment. However, the gene expression of the cytokine TNF-α increased in fish fed the methionine-deficient diet, indicative of stressful conditions in the liver. Even though taurine concentrations in the liver were not affected by treatment, methionine and taurine concentrations in muscle decreased due to methionine deficiency. Concomitantly, liver phospholipid and cholesterol concentrations were reduced, while NEFA concentrations were elevated. In conclusion, methionine deficiency did not increase polyamine turnover through depletion of hepatic SAM, as assessed by SSAT activity and abundance.

Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats

Respiratory distress and bronchopulmonary dysplasia (BPD) are major problems in preterm infants that are often addressed by glucocorticoid treatment and increased oxygen supply, causing catabolic and injurious side effects. Recombinant human keratinocyte growth factor (rhKGF) is noncatabolic and antiapoptotic and increases surfactant pools in immature lungs. Despite its usefulness in injured neonatal lungs, the mechanisms of improved surfactant homeostasis in vivo and systemic effects on lipid homeostasis are unknown. We therefore exposed newborn rats to 85% vs. 21% oxygen and treated them systemically with rhKGF for 48 h before death at 7 days. We determined type II pneumocyte (PN-II) proliferation, surfactant protein (SP) mRNA expression, and the pulmonary metabolism of individual phosphatidylcholine (PC) species using [D9-methyl]choline and tandem mass spectrometry. In addition, we assessed liver and plasma lipid metabolism, addressing PC synthesis de novo, the liver-specific phosphatidylethanolamine methyl transferase (PEMT) pathway, and triglyceride concentrations. rhKGF was found to maintain PN-II proliferation and increased SP-B/C expression and surfactant PC in both normoxic and hyperoxic lungs. We found increased total PC together with decreased [D9-methyl]choline enrichment, suggesting decreased turnover rather than increased secretion and synthesis as the underlying mechanism. In the liver, rhKGF increased PC synthesis, both de novo and via PEMT, underlining the organotypic differences of rhKGF actions on lipid metabolism. rhKGF increased the hepatic secretion of newly synthesized polyunsaturated PC, indicating improved systemic supply with choline and essential fatty acids. We suggest that rhKGF has potential as a therapeutic agent in neonates by improving pulmonary and systemic PC homeostasis.