Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet.

High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon.

Replacing fish oil and astaxanthin by microalgal sources produced different metabolic responses in juvenile rainbow trout fed 2 types of practical diets.

Dietary fish oil supplementation provides n-3 long-chained polyunsaturated fatty acids for supporting fish growth and metabolism and enriching fillet with eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; c22:6n-3). Two experiments were performed as a 3 × 2 factorial arrangement of dietary treatments for 16 wk to determine effects and mechanisms of replacing 0%, 50%, and 100% fish oil with DHA-rich microalgae in combination with synthetic vs. microalgal source of astaxanthin in plant protein meal (PM)- or fishmeal (FM)- based diets for juvenile rainbow trout (Oncorhynchus mykiss). Fish (22 ± 0.26 g) were stocked at 17/tank and 3 tanks/diet. The 100% fish oil replacement impaired (P < 0.0001) growth performance, dietary protein and energy utilization, body indices, and tissue accumulation of DHA and EPA in both diet series. The impairments were associated (P < 0.05) with upregulation of hepatic gene expression related to growth (ghr1and igf1) and biosynthesis of DHA and EPA (fads6 and evol5) that was more dramatic in the FM than PM diet-fed fish, and more pronounced on tissue EPA than DHA concentrations. The source of astaxanthin exerted interaction effects with the fish oil replacement on several measures including muscle total cholesterol concentrations. In conclusion, replacing fish oil by the DHA-rich microalgae produced more negative metabolic responses than the substitution of synthetic astaxanthin by the microalgal source in juvenile rainbow trout fed 2 types of practical diets.

Dietary supplemental microalgal astaxanthin modulates molecular profiles of stress, inflammation, and lipid metabolism in broiler chickens and laying hens under high ambient temperatures.

This research was to determine effects of supplemental dietary microalgal astaxanthin (AST) on hepatic gene expression and protein production of redox enzymes, heat shock proteins (HSPs), cytokines, and lipid metabolism in broilers (BR) and laying hens (LH) under high ambient temperatures. A total of 240 (day old) Cornish male BR and 50 (19 wk old) White Leghorn Shavers LH were allotted in 5 dietary treatments with 6 and 10 cages/treatment (8 BR or 1 LH/cage), respectively. The birds were fed corn-soybean meal basal diets supplemented with microalgal (Haematococcus pluvialis) AST at 0, 10, 20, 40, and 80 mg/kg diet for 6 wk. Supplemental AST to the BR diet linearly decreased (P < 0.10, R2 = 0.18-0.36) hepatic mRNA levels of several redox status-controlling genes, heat shock protein 70 (HSP70), heat shock transcription factor 1 (HSTF1), c-Jun N-terminal kinase 1 (JNK1), tumor necrosis factor-α, and sterol regulatory element-binding protein 1 (SREBP1). The supplementation linearly elevated (P = 0.04, R2 = 0.20) diacylglycerol acyltransferase 2 (DGAT2) mRNA level and produced quadratic changes (P < 0.10, R2 = 0.15-0.47) in mRNA levels of glutathione S-transferase (GST), serine/threonine kinase (AKT1), P38 mitogen-activated protein kinase (P38MAKP), lipid metabolism-controlling genes, and the protein production of HSP90 and P38MAPK in the liver. Supplementing AST to the LH diets linearly decreased (P < 0.10, R2 = 0.18-0.56) mRNA levels of GST, HSF1, JNK1, and interleukin 10; lipogenesis genes; and JNK1 protein production. However, supplemental dietary AST produced quadratic changes (P < 0.10, R2 = 0.26-0.72) in mRNA levels of most antioxidant-, stress-responsive, and lipid metabolism-related genes in the liver of LH. In conclusion, supplemental dietary AST affected the hepatic gene expression and protein production related to redox status, heat stress and inflammation, and lipid metabolism in both BR and LH. The impacts varied with the chicken type and demonstrated linear and quadratic regressions with the inclusion levels of AST.

Supplemental methionine and stocking density affect antioxidant status, fatty acid profiles, and growth performance of broiler chickens.

Broilers stocked in high densities may be prone to oxidative and inflammatory insults, resulting in impaired health status, growth performance, and meat quality. This study was to determine if 30% extra supplemental dl-methionine alleviated or prevented those adverse effects of a higher stocking density in broiler chickens. A total of 560 male Cornish Cross cockerels (day old) were divided into four groups: two stocking densities (9 and 12 birds/m2) and two supplementations of methionine (grower: 2.90 or 3.77 g/kg and finisher: 2.60 or 3.38 g/kg). Growth performance was recorded weekly. Blood and tissues were sampled at the end of each period. High stocking density decreased (P < 0.05) body weight and growth performance of growers and (or) finishers. Those differences were partially attenuated by the extra methionine supplementation. The high methionine elevated (P < 0.05) glutathione (GSH) concentration in the thigh at both ages (> 24%). The high stocking density elevated (>28%, P < 0.05) glutathione concentration in the plasma, breast, and thigh of growers, but decreased (P < 0.05) it in the liver of growers and thigh of finishers. Interaction effects (P < 0.05) between dietary methionine and stocking density were found on activities of the antioxidant enzyme glutathione S-transferase in the liver of growers and breast, thigh, and adipose tissue of finishers. The interaction effect was also found on activities of glutathione peroxidase and superoxide dismutase in the thigh of growers. The extra methionine decreased (P < 0.05) hepatic gene expression of heat shock protein 90 (18%) and thigh and breast malondialdehyde concentrations of the finishers (35%). In conclusion, the 30% extra dl-methionine supplementation was able to partially mitigate adverse effects caused by the higher stocking density and to improve the redox status of the broilers.

Supplemental methionine exerted chemical form-dependent effects on antioxidant status, inflammation-related gene expression, and fatty acid profiles of broiler chicks raised at high ambient temperature1.

This study was to explore metabolic effects of two forms and concentrations of supplemental methionine in grower and finisher diets for broiler chickens raised at high temperature. Male Cornish cockerel chicks (total = 360, day-old) were divided into four groups (10 pens/treatment, 9 chicks/pen) and fed with 100% or 130% required methionine in the diets as DL-methionine (DL-MET) or 2-hydroxy-4-(methylthio)butanoate (HMTBA). The room was maintained at 4 to 13 °C above the suggested thermoneutral temperature. The higher concentration of both DL-MET and HMTBA enhanced (P < 0.05) hepatic GSH concentrations of the growers and plasma ferric reducing ability of the finishers. The DL-MET-fed growers had greater (P < 0.05%) muscle GSH and hepatic unsaturated fatty acid concentrations than those fed HMTBA. Expression of inflammation-related genes in the liver of finishers was affected (P < 0.05) by interaction effects of the methionine form and concentration. In conclusion, effects of the extra methionine supplementation on the high ambient temperature-related metabolic responses of broilers varied with their age and(or) tissue and the methionine form.

Defatted Microalgae-Mediated Enrichment of n-3 Polyunsaturated Fatty Acids in Chicken Muscle Is Not Affected by Dietary Selenium, Vitamin E, or Corn Oil.

Background: We previously showed enrichments of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in broiler chicks fed defatted microalgae. Objectives: The aims of this study were to determine 1) if the enrichments affected meat texture and were enhanced by manipulating dietary corn oil, selenium, and vitamin E concentrations and 2) how the enrichments corroborated with hepatic gene expression involved in biosynthesis and oxidation of EPA and DHA. Methods: Day-old hatching Cornish Giant cockerels (n = 216) were divided into 6 groups (6 cages/group and 6 chicks/cage). Chicks were fed 1 of the 6 diets: a control diet containing 4% corn oil, 25 IU vitamin E/kg, and 0.2 mg Se/kg (4CO), 4CO + 10% microalgae (defatted Nannochloropsis oceanica; 4CO+ MA), 4CO+ MA - 2% corn oil (2CO+MA), 2CO+MA + 75 IU vitamin E/kg (2CO+MA+E), 2CO+MA + 0.3 mg Se/kg (2CO+MA+Se), and 2CO+MA+E + 0.3 mg Se/kg (2CO+MA+E+Se). After 6 wk, fatty acid profiles, DHA and EPA biosynthesis and oxidation, gene expression, lipid peroxidation, antioxidant status, and meat texture were measured in liver, muscles, or both. Results: Compared with the control diet, defatted microalgae (4CO+MA) enriched (P < 0.05) DHA and EPA by ≤116 and 24 mg/100 g tissue in the liver and muscles, respectively, and downregulated (41-76%, P < 0.01) hepatic mRNA abundance of 4 cytochrome P450 (CYP) enzymes (CYP2C23b, CYP2D6, CYP3A5, CYP4V2). Supplemental microalgae decreased (50-82%, P < 0.05) lipid peroxidation and improved (16-28%, P < 0.05) antioxidant status in the liver, muscles, or both. However, the microalgae-mediated enrichments in the muscles were not elevated by altering dietary corn oil, vitamin E, or selenium and did not affect meat texture. Conclusion: The microalgae-mediated enrichments of DHA and EPA in the chicken muscles were associated with decreased hepatic gene expression of their oxidation, but were not further enhanced by altering dietary corn oil, vitamin E, or selenium.

Dose-Dependent Enrichments and Improved Redox Status in Tissues of Broiler Chicks under Heat Stress by Dietary Supplemental Microalgal Astaxanthin.

Astaxanthin (AST) is a well-known carotenoid with a high antioxidant capacity. This study was designed to evaluate the nutritional and metabolic effects of microalgal AST added to the diets of broiler chicks under heat stress. A total of 240 Cornish male chicks (1 day old) were divided into six cages per treatment (eight chicks per cage) and fed a corn-soybean meal diet supplemented with AST from Haematococcus pluvialis at 0, 10, 20, 40, and 80 mg/kg for 6 weeks. Heat stress was employed during weeks 4-6. The supplementation led to dose-dependent enrichments ( P < 0.05) of AST and total carotenoids in the plasma, the liver, and the breast and thigh muscles. There were similar enhancements ( P < 0.05) of oxygen-radical-absorbance capacities, but there were decreases or mixed responses ( P < 0.05) of glutathione concentrations and glutathione peroxidase activities in the tissues. In conclusion, supplemental dietary microalgal AST was bioavailable to the chicks and enriched in their tissues independent of heat stress, leading to coordinated changes in their endogenous antioxidant defense and meat quality.