Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFα

Purpose

The beneficial effects of a seafood-rich diet are highly documented and can be attributed to both n-3 polyunsaturated fatty acids and other less studied nutritional components including protein and antioxidants. The aim of the work was to investigate whether an under-utilized seafood source, eggs (roe) and sperm (milt) from herring (Clupea harengus), can affect lipid metabolism and inflammation in a mouse model transgenic for human tumor necrosis factor alpha (hTNFα).

Methods

A high-fat control diet (25% total fats, 20% protein, w/w) or high-fat diets supplemented with herring roe (3.7% fat, 15% protein, w/w), or milt (1.3% fat, 15% protein) were administered to female C57BL/6 hTNFα mice. After 2?weeks, hepatic enzyme activity, gene expression, lipid and fatty acid composition, fatty acid composition of epididymal adipose tissue, and plasma lipid and cytokine levels were determined.

Results

Animals fed herring roe and milt displayed an increased hepatic fatty acid β-oxidation and reduced fatty acid synthase activity. However, while plasma TAG was reduced, hepatic TAG and plasma and hepatic cholesterol levels were increased by the herring diets. Both herring diets led to a substantial shift in the n-6:n-3 ratio in both liver and ovarian white adipose tissue. The herring diets also increased plasma carnitine and reduced the carnitine precursor trimethyllysine. Plasma short-chained acylcarnitine esters were significantly increased, which may reflect an increased β-oxidation of long-chained fatty acids. In addition, the diets tended to reduce the plasma levels of pro-inflammatory cytokines.

Conclusion

Herring roe or milt diets enhanced lipid catabolism and influenced the chronic inflammatory state in hTNFα-transgenic mice.     

Is the effect of high fat diet on lipid and carbohydrate metabolism related to inflammation?

Obesity is an emerging health problem in world wide countries. High fat diet (HFD), which is the main cause of obesity, induces inflammation and affects both lipid and carbohydrate metabolism. This study investigates the effect of inflammation induced by HFD on lipid and carbohydrate metabolism. This study involves two parts, in vivo and in vitro. In the in vivo part, adult male albino rats were fed a HFD for 8 and 14 weeks. After each feeding period, the following parameters were measured (body weight, blood glucose levels, oral glucose tolerance, serum insulin, insulin resistance, total cholesterol, HDLc, LDLc, triglycerides, free fatty acids, neutrophils percentage and serum CRP levels) in addition to pancreas tissue histopathology. In the in vitro part, insulin release from isolated perfused pancreas preparations was measured. Pancreas preparations were isolated from adult male albino rats fed a HFD for 16 weeks. Feeding rats a HFD for 8 and 14 weeks induced inflammation, impaired lipid profile and carbohydrate metabolism. Feeding rats a HFD for 16 weeks increased in vitro glucose-stimulated insulin release. HFD induces inflammation which plays an important role in the impairment of lipid and carbohydrate metabolism.     

Molecular analysis of Helicobacter pylori-associated gastric inflammation in naïve versus previously immunized mice

To identify mechanisms of immunity against Helicobacter pylori, we performed microarray analysis on gastric tissue from infected mice and mice vaccinated prior to challenge. RNA from gastric tissue was used to screen over 10,000 genes. MHC antigens and GTP binding proteins were upregulated in both groups. Infected mice were characterized by expression of innate host defense markers while immune mice expressed many IFN-gamma response genes and T cell markers. Results were confirmed for several genes by RT-PCR. CD4+ spleen cells from immune mice produced significantly more IFN-gamma than from infected mice. These results support a role for T cell regulated inflammation in H. pylori immunity.     

Effects of d-α-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-α and PPAR-γ. We investigated the effects of d-α-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-α and PPAR-γ in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-α-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-α-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-α expression and decreasing PPAR-γ expression. In conclusion, the oral administration of d-α-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-α and PPAR-γ in a high-fat diet-fed male mice.     

Dietary versus post-mortem use of oregano oil and/or α-tocopherol in turkeys to inhibit development of lipid oxidation in meat during refrigerated storage

The dietary and post-mortem uses of oregano oil in turkeys to inhibit development of lipid oxidation in breast and thigh meat during refrigerated storage were investigated. Using minced meat, patties were prepared from turkey meat post-mortem added with either 200 mg oregano oil or α-tocopherol/kg, meat from turkeys dietary supplemented with either 200 mg oregano oil or α-tocopheryl acetate/kg feed, and control meat. All patties were cooked, placed in a refrigerated cabinet at 4°C, and lipid oxidation was assessed by monitoring malondialdehyde formation after 3, 6 and 9 days of storage. Treatments significantly (P<0.05) retarded lipid oxidation in both breast and thigh meat patties at all storage times compared with controls. The dietary supplementation of either oregano oil or α-tocopheryl acetate exhibited the highest antioxidative activity compared with the other treatments. Post-mortem addition of either oregano oil or α-tocopherol to the minced meat also retarded lipid oxidation in the prepared patties compared with controls; however, this effect was inferior to that of the dietary supplementation even though the post-mortem α-tocopherol supplemented meat contained 90-fold more α-tocopherol than patties from the dietary supplemented meat. Thigh meat was more susceptible to oxidation than breast meat, although the former contained α-tocopherol at markedly higher levels. Supplementing the diet with 200 mg oregano oil/kg, α-tocopherol levels in the breast and thigh meat significantly (P<0.05) increased compared with control. This increase could not be attributed to the α-tocopherol already present in the oregano oil since post-mortem addition of oregano oil to control breast and thigh meat at the same dose could not actually increase the α-tocopherol concentrations.     

Hepatic lipid metabolism response to dietary fatty acids is differently modulated by PPARα in male and female mice

Background  

In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids.     

Successful treatment of parenteral nutrition–associated liver disease in an adult by use of a fish oil–based lipid source

Liver disease occurs in 15% to 40% of adults on long-term parenteral nutrition, with steatosis being more common than cholestasis in the adult population. This problem has been well reported in the pediatric population, but we describe the case of a man who became profoundly jaundiced after being on parenteral nutrition for 3 y and responded rapidly to a change in lipid source from soybean and olive oil–based emulsion (ClinOleic) to a fish oil–based lipid emulsion (Omegaven).     

Comparison of ultraviolet light‐induced skin carcinogenesis and ornithine decarboxylase activity in Sencar and Hairless SKH‐1 mice fed a constant level of dietary lipid varying in corn and coconut oil

To investigate the effect of various levels of corn oil and coconut oil on ultraviolet (UV) light‐induced skin tumorigenesis and ornithine decarboxylase (ODC) activity, Sencar and SKH‐1 mice were fed one of three 15% (weight) fat semipurified diets containing three ratios of com oil to coconut oil: 1.0%:14.0%, 7.9%:7.1%, and 15.0%:0.0% in Diets A, B, and C, respectively. Groups of 30 Sencar and SKH‐1 mice were fed one of the diets for three weeks before UV irradiation; then both strains were UV irradiated with an initial dose of 90 mJ/cm². The dose was given three times a week and increased 25% each week. For Sencar mice (irradiated 33 wks for a total dose of 48 J/cm²), tumor incidence reached a maximum of 60%, 60%, and 53% for Diets A, B, and C, respectively, with an overall average of one to two tumors per tumor‐bearing animal. For the SKH‐1 mice (irradiated 29 wks for a total dose of 18 J/cm²), all diet groups reached 100% incidence by 29 weeks, with approximately 12 tumors per tumor‐bearing mouse. No significant effect of dietary corn oil/coconut oil was found for tumor latency, incidence, or yield in either strain. The effect of increasing com oil on epidermal ODC activity in chronically UV‐irradiated Sencar and SKH‐1 mice was assessed Three groups of mice from each strain were fed one of the experimental diets and UV irradiated for six weeks. Sencar mice showed no increase in ODC activity until six weeks of treatment, when the levels of ODC activity in the UV‐irradiated mice fed Diet A were significantly higher than those in mice fed Diet B or Diet C: 1.27, 0.55, and 0.52 nmol/mg protein/hr, respectively. In the SKH‐1 mice, ODC activity was increased by the first week of UV treatment, and by three weeks of treatment a dietary effect was observed: ODC activity was significantly higher in mice fed Diet C (0.70 nmol/mg protein/hr) than in mice fed Diet A (0.18 nmol/mg protein/hr). Although there was no significant effect of dietary corn oil/coconut oil on UV‐induced tumor incidence, the data indicate that chronically UV‐irradiated hairless SKH‐1 mice are more susceptible to UV‐induced skin carcinogenesis than Sencar mice and that this susceptibility is correlated with increases in ODC activity, a parameter of cell proliferation.     

Apple flavonols and n-3 polyunsaturated fatty acid–rich fish oil lowers blood C-reactive protein in rats with hypercholesterolemia and acute inflammation

Both quercetin glycosides and omega-3 polyunsaturated fatty acids (n-3 PUFA) are well established for their individual health benefits in ameliorating metabolic disease. However, their combined effects are not well documented. It was hypothesized that the beneficial properties of quercetin glycosides can be enhanced when provided in combination with n-3 PUFA. Therefore, the aim of the present study was to investigate the effects of apple flavonols (AF) and fish oil (FO), alone and in combination, on proinflammatory biomarkers and lipid profiles in rats fed a high-fat diet. Sixty male Wistar rats were randomly divided into 5 groups (n = 12) and fed a high-fat diet for 4 weeks. One of the 5 groups of rats was used as the high-fat control. The other 4 groups of rats were injected with lipopolysaccharide (LPS) (5 mg/kg body weight) intraperitoneally, 5 hours before euthanization. One of these 4 groups was used as the hypercholerolemic and inflammatory control (high-fat with lipopolysaccharide [HFL]), and the other 3 received AF (HFL + 25 mg/kg per day AF), FO (HFL + 1 g/kg per day FO), or the combination (HFL + AF + FO). Compared to the HFL group, the AF, FO, and AF + FO groups showed lower serum concentrations of interleukin-6 and C-reactive protein (CRP) levels. The AF, FO, and AF + FO also had lowered serum triacylglycerol and non–high-density lipoprotein cholesterol (HDL-C) concentrations, but higher HDL-C levels relative to the HFL group. An additive effect was observed on serum CRP in the AF + FO group as compared with the AF or FO groups. The results demonstrated that AF and FO inhibited the production of proinflammatory mediators and showed an improved efficacy to lower serum CRP when administered in combination, and they significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and LPS-induced acute inflammation.     

Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10(-/-) model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10(-/-) mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.     

Regulation of iron metabolism in Hamp −/− mice in response to iron-deficient diet

Background

Hepcidin, the liver-secreted iron regulatory peptide, maintains systemic iron homeostasis in response to several stimuli including dietary iron levels and body iron status. In addition, iron metabolism is controlled by several local regulatory mechanisms including IRP and Hif-2α activities independently of hepcidin. However, the roles of these mechanisms and their interaction particularly in hepcidin-deficient individuals are not yet fully understood. We, therefore, aimed to explore whether Hamp disruption affects iron homeostatic responses to dietary iron deficiency.

Methods

Hepcidin1 knockout (Hamp ^?/?) mice and heterozygous littermates were fed with control or iron-deficient diet for 2 weeks. The expression of iron-related genes and proteins were determined by quantitative PCR and Western blot, respectively.

Results

Two-week iron-deficient diet feeding in Hamp ^?/? mice did not alter serum iron but significantly reduced liver non-heme iron levels. This was also associated with increased ferroportin protein expression in the duodenum and spleen, whereas decreased expression was found in the liver. In addition, significant inductive effects of iron-deficient diet on Dcytb and DMT1 mRNA expression in the duodenum were noted with more pronounced effects in Hamp ^?/? mice compared with controls.

Conclusions

Hamp ^?/? mice exhibited a more dramatic increase in the expression of iron transport machinery, which may be responsible for the unaltered serum iron levels upon iron-deficient diet feeding in these mice. Despite the lack of hepcidin, Hamp ^?/? mice can maintain a degree of iron homeostasis in response to altered dietary iron through several hepcidin-independent mechanisms.     

High α-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats

Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high–n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis.     

Vitamin a status and metabolism of benzo[α]pyrene in the rat

Male Sprague‐Dawley rats were maintained on a vitamin A‐deficient diet for a period of five weeks. At the end of that time, hepatic cytochrome P₄₅₀ levels in vitamin A‐deficient rats were 65% that of rats fed a complete diet. However, the hepatic rate of benzo[a]pyrene metabolism was significantly greater (2 times) in vitamin A‐deficient rats compared with those fed a complete diet. The pattern of metabolites separable by thin‐layer chromatography was similar in both groups of rats. Benzo[a]pyrene induced its own metabolism by a slightly greater amount in the vitamin‐sufficient rats, but it was not to the level of the deficient group, although the levels of cytochrome P₄₅₀ were still below those of the deficient rats. In discussing lung microsomes, benzo[a]pyrene pre‐treatment of deficient rats resulted in slightly elevated levels of cytochrome P₄₅₀ and a slightly greater rate of metabolism of benzo[a]pyrene compared with rats fed the complete diet.     

Do glucose and lipid metabolism affect cancer development in Nagasaki atomic bomb survivors?

The relationship between lipid or glucose metabolism and cancer has not yet been elucidated. We conducted 75-g oral glucose tolerance tests (75-g OGTTs) and lipid measurements between 1983 and 1985 in 516 Nagasaki atomic bomb survivors. Excluding those who already had cancer at the baseline examinations and those who developed cancers or died of any cause within 5 yr after the baseline examinations, we determined incident cancer cases until 2000 in the remaining 451 subjects (214 males and 237 females) and evaluated, by means of the Cox proportional hazard model, whether glucose or lipid metabolism predicts cancer development. The age- and sex-adjusted relative risk (RR) for incident cancer was 0.903 (95% confidence interval, CI = 0.842-0.968), 1.740 (95% CI = 1.238-2.446), 1.653 (95% CI = 0.922-2.965), and 1.024 (95% CI = 0.996-1.053) for total cholesterol (10 mg/dl), radiation dose (1 Sv), smoking, and 1-h blood glucose (1-h BG; 10 mg/dl) in 75-g OGTTs, respectively. Multiple regression analysis of age, sex, smoking, body mass index, 1-h BG, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and radiation dose also showed that total cholesterol was negatively (RR = 0.872; 95% CI = 0.793-0.958) and radiation dose positively (RR = 1.809; 95% CI = 1.252-2.613) related to incident cancer. Cholesterol could be negatively and radiation dose positively associated with cancer development independently.     

Gut–brain and brain–gut axis in Parkinson's disease models: Effects of a uridine and fish oil diet

Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The ‘dual-hit’ hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this ‘dual-hit hypothesis’ and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1?week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD.