Supplemental 25-hydroxycholecalciferol Alleviates Inflammation and Cardiac Fibrosis in Hens.

Broiler breeder hens with efficient feed conversion rate under restricted feed intake (R-hens) or allowed unlimited access to feed (Ad-hens) progressed with cardiac functional failure and suffered early sudden death. A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed improved heart health and rescued livability in both R- and Ad-hens throughout laying stage (26-60 wks). Improvements occurred through cardiac hypertrophic remodeling, reduced arrhythmias, and pathological cues. Here, we further demonstrated consistently decreased circulating and cardiac IL-6 and IL-1ß levels in conjunction with reduced cardiac chemoattraction and leukocyte infiltration by 25-OH-D3 in Ad-hens and in R-hens at later time points (35 and 47 wks) (p < 0.05). Supplemental 25-OH-D3 also ameliorated cardiac fibrosis, endoplasmic reticulum (ER) stress, and autophagy, mostly in Ad-hens, as both collagen content and expression of COL3A1, as well as CCAAT box binding enhancer homologous protein (CHOP) and activating transcription factor 6 (ATF6), were consistently decreased, and suppression of microtubule-associated protein 1 light Chain 3 beta (LC3B) and Sequestosome 1 (SQSTM1) was rescued at 35 and 47 wks (p < 0.05). Vitamin D receptor-NF-κB signaling was shown to mediate these beneficial effects. The present results demonstrate that ER stress and autophagic processes along the sequence from inflammation to fibrotic changes contribute to pathological cardiac remodeling and functional compromise by Ad-feed intake. 25-OH-D3 is an effective anti-inflammatory and anti-fibrotic supplement to ameliorate cardiac pathogenesis in broiler breeder hens.

Dietary supplementation of 25-hydroxycholecalciferol improves cardiac function and livability in broiler breeder hens-amelioration of blood pressure and vascular remodeling.

A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed suppressed the mortality in feed-restricted broiler breeder hens and in hens allowed ad libitum feed intake (Ad-hens) in a feeding trial from age 26 to 60 wk. Outcomes for the mechanisms found that 25-OH-D3 relieved systemic hypoxia, pathological cardiac remodeling and arrhythmias, and hepatopathology to improve hens' livability. In the study, we further evaluated the effect of 25-OH-D3 on blood pressure and vascular remodeling relative to cardiac pathogenesis of sudden death (SD). Ad libitum feed intake increased mechanical loading and contributed to maladaptive cardiac hypertrophy as evidenced by consistently elevated peripheral arterial blood pressure in Ad-hens before SD (P < 0.05). In planned longitudinal measurements, Ad-hens also showed higher right ventricle systolic pressure and right ventricle diastolic pressure (RVDP) (P < 0.05). Supplemental 25-OH-D3 relieved peripheral hypertension and prevented time-dependent increases of RVDP in Ad-hens through the renin-angiotensin system and circulating nitric oxide availability and by regulating vascular remodeling including elastin/collagen ratio and smooth muscle cell proliferation in the pulmonary artery for improved elasticity/stiffness (P < 0.05). The antihypertensive effect via the renin-angiotensin system and nitric oxide regulation in respect to heart rate and arrhythmias by 25-OH-D3 were further confirmed in 51 week-old feed-restricted broiler breeder hens challenged with salt loading for 5 wk. Despite feed restriction, the most feed-efficient hens of feed-restricted groups also exhibited cardiac pathological hypertrophy, in conjunction with higher right ventricle systolic pressure, RVDP, plasma nitric oxide levels, and more dramatic arterial remodeling (P < 0.05). These results suggest that peripheral and pulmonary hypertension are the key drivers of SD and that 25-OH-D3 is an effective antihypertensive supplement to alleviate cardiac pathogenesis and improve livability in broiler breeder hens.

Dietary supplementation of 25-hydroxycholecalciferol improves livability in broiler breeder hens.

The study aimed to examine the effects of 25-hydroxycholecalciferol (25-OH-D3) on reproductive performance and livability in broiler breeder hens. Hens at age of 26 wk were continued on restricted rations (R) or allowed ad libitum feeding (Ad) to 60 wk of age. Ad-feed intake greatly impaired egg production and hens' livability. The survival rate in both R- and Ad-hens was improved (86.7 vs.78.9% and 48.2 vs.29.1%, respectively) as was egg production in R-hens (P < 0.05) by inclusion of 69 µg 25-OH-D3/kg feedin the basal diet. Sudden death (SD) was the cause of hen mortality; hens died earlier with heavier BW and greater absolute and relative abdominal fat weights than surviving hens. Interestingly, feed intake of SD hens became less than that of surviving hens after 37 and 42 wk in Ad- and R-groups, respectively, and led to a progressive decline in SD hen BW with a ratio (relative to surviving hens of the same age) equaled 1 around 34 to 38 wk in Ad-groups and 52 to 53 wk in R-groups. Supplementation of 25-OH-D3 ameliorated untoward changes of heart and respiratory rate of Ad-survivors after 29 wk (P < 0.05), but had no significant effects on SD AD-hens. In contrast to the surviving counterparts, all SD hens experienced persistently higher respiratory rates in conjunction with declining heart rates (P < 0.05), suggesting compromised cardiac function as the cause of SD, in which hens increased heart and respiratory rate for more blood and oxygen supply to meet the need for rapid BW gain and/or adiposity in response to Ad-feed intake or due to genetically better feed efficiency even under R-feed intake. As the cardiorespiratory derangements advanced, compromised cardiac function ultimately led to heart failure and sudden death despite spontaneous reductions in feed intake and BW loss in all SD hens. Provision of 69 µg 25-OH-D3/kg feed is an effective and practical method to improve livability in broiler breeder hens.

Palmitoleate induces hepatic steatosis but suppresses liver inflammatory response in mice.

The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16:1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD.

Consumption of high-oleic acid ground beef increases HDL-cholesterol concentration but both high- and low-oleic acid ground beef decrease HDL particle diameter in normocholesterolemic men.

On the basis of previous results from this laboratory, this study tested the hypothesis that ground beef high in MUFA and low in SFA would increase the HDL-cholesterol (HDL-C) concentration and LDL particle diameter. In a crossover dietary intervention, 27 free-living normocholesterolemic men completed treatments in which five 114-g ground beef patties/wk were consumed for 5 wk with an intervening 4-wk washout period. Patties contained 24% total fat with a MUFA:SFA ratio of either 0.71 (low MUFA, from pasture-fed cattle) or 1.10 (high MUFA, from grain-fed cattle). High-MUFA ground beef provided 3.21 g more 18:1(n-9), 1.26 g less 18:0, 0.89 g less 16:0, and 0.36 g less 18:1(trans) fatty acids per patty than did the low-MUFA ground beef. Both ground beef interventions decreased plasma insulin and HDL(2) and HDL(3) particle diameters and increased plasma 18:0 and 20:4(n-6) (all P ≤ 0.05) relative to baseline values. Only the high-MUFA ground beef intervention increased the HDL-C concentration from baseline (P = 0.02). The plasma TG concentration was positively correlated with the plasma insulin concentration (r = 0.40; P < 0.001) and negatively correlated with HDL-C (r = -0.47; P < 0.001) and plasma 18:0 (r = -0.24; P < 0.01). Plasma insulin and HDL diameters were not correlated (r = 0.01; P > 0.50), indicating that reductions in these measures were not coordinately regulated. The data indicate that dietary beef interventions have effects on risk factors for cardiovascular disease that are independent (insulin, HDL diameters) and dependent (HDL-C) on beef fatty acid composition.

Characterization of very-low density lipoprotein particle diameter dynamics in relation to egg production in a passerine bird.

During avian egg production, oestrogen mediates marked increases in hepatic lipid production and changes in the diameter of assembled very-low density lipoprotein (VLDL). A nearly complete shift from generic VLDL ( approximately 70 nm in diameter), which transports lipids to peripheral tissues, to yolk-targeted VLDL (VLDLy) ( approximately 30 nm), which supplies the yolk with energy-rich lipid, has been observed in the plasma of laying domestic fowl. We validated an established dynamic laser scattering technique for a passerine songbird Taeniopygia guttata, the zebra finch, to characterize the dynamics of VLDL particle diameter distribution in relation to egg production. We predicted that non-gallinaceous avian species that have not been selected for maximum egg production would exhibit less dramatic shifts in lipid metabolism during egg production. As predicted, there was considerable overlap between the VLDL particle diameter distributions of laying and non-laying zebra finches. But unexpectedly, non-laying zebra finches had VLDL diameter distributions that peaked at small particles and had relatively few large VLDL particles. As a result, laying zebra finches, in comparison, had diameter distributions that were shifted towards larger VLDL particles. Nevertheless, laying zebra finches, like laying chickens, had larger proportions of particles within proposed VLDLy particle diameter ranges than non-laying zebra finches (e.g. sVLDLy: 50% vs 37%). Furthermore, zebra finches and chickens had similar modal (29.7 nm in both species) and median (32.7 nm vs 29.6 nm) VLDL particle diameters during egg production. Therefore, although zebra finches and chickens exhibited opposing directional shifts in VLDL particle diameter distribution during egg production, the modifications to VLDL particle structure in both species resulted in the realization of a common goal, i.e. to produce and maintain a large proportion of small VLDL particles of specific diameters that are capable of being incorporated into newly forming egg yolks.