A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.

A 2 x 2 factorial continuous experiment was conducted with 28 Norwegian Red dairy cows in early lactation to compare milk content of phytoestrogens when feeding ad libitum white clover (WCS) or red clover (RCS) grass silages prepared from the second and third cut without and with 10 kg/d supplementation of a standard concentrate. The cows were offered either RCS or WCS for 88 d (period 1) and thereafter a mixed red clover-white clover-grass silage for 48 d (period 2). Total dry matter intake and milk yield were not affected by forage type but increased with concentrate supplementation. Intake of isoflavones was several times greater in RCS than in WCS, whereas intake of lignans was greater in WCS. Concentrate supplementation reduced the intake of most phytoestrogens. Compared with WCS, RCS diets yielded milk with a greater content of flavonoids, whereas milk from WCS diets had greater contents of the mammalian lignans enterodiol and enterolactone. The content of the isoflavan equol was particularly high in RCS diets. There was no apparent carryover effect of clover type on milk phytoestrogen content because there was no difference in content between the silage treatments 3 wk after the cows were transferred to the same silage diet (period 2). Concentrate supplementation reduced the milk contents of the flavonoids equol, biochanin A, and daidzein and increased the content of mammalian lignans. The effects of silage type and concentrate supplementation on milk contents of the individual phytoestrogens were related to the intake of the compound or its precursor, except for the effect of concentrate on mammalian lignans, for which the intake of the known precursors was also reduced. Overall, this study shows that feeding cows with silage containing red clover increases the milk content of flavonoids at both low and high concentrate supplementation levels, and decreases the content of nonflavonoids such as mammalian lignans, when compared with silage containing white clover. The increased content of phytoestrogens in milk may be important when the health benefits of milk are studied.

The concentration-dependent activity of the polyacetylene falcarinol ((9Z)-heptadeca-1,9-dien-4,6-diyn-3-ol), isolated from carrots, was investigated in a bioassay with primary mammary epithelial cells in collagen gels and compared with that of β-carotene, the orange pigment in carrots. Falcarinol showed biphasic activity, having stimulatory effects between 0.01 and 0.05 µg ml −1 and inhibitory effects between 1 and 10 µg ml −1 , whereas β-carotene showed no effect in the concentration range 0.001-100 µg ml −1 . The results are discussed in relation to the health-promoting effects of carrots and related vegetables. Falcarinol was quantified in the carrot cultivars Bolero, Rodelika and Fancy by analytical reverse phase HPLC, subjected to various processing and storage conditions in order to study how long-term storage, blanching, freezing and boiling influence the content of falcarinol. Long-term storage of raw carrot cubes (1 cm 3 ) reduced the falcarinol content by almost 35%. A similar reduction was found in steam-blanched carrot cubes (1 cm 3 ). Long-term storage at −24 • C of steam blanched carrot cubes did not reduce the falcarinol content further. A reduction of almost 70% in the falcarinol content was found in carrot pieces boiled in water for 12 min compared with raw carrots.

Lack of animal models with human-like size and pathology hampers translational research in atherosclerosis. Mouse models are missing central features of human atherosclerosis and are too small for intravascular procedures and imaging. Modeling the disease in minipigs may overcome these limitations, but it has proven difficult to induce rapid atherosclerosis in normal pigs by high-fat feeding alone, and genetically modified models similar to those created in mice are not available. D374Y gain-of-function mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause severe autosomal dominant hypercholesterolemia and accelerates atherosclerosis in humans. Using Sleeping Beauty DNA transposition and cloning by somatic cell nuclear transfer, we created Yucatan minipigs with liver-specific expression of human D374Y-PCSK9. D374Y-PCSK9 transgenic pigs displayed reduced hepatic low-density lipoprotein (LDL) receptor levels, impaired LDL clearance, severe hypercholesterolemia, and spontaneous development of progressive atherosclerotic lesions that could be visualized by noninvasive imaging. This model should prove useful for several types of translational research in atherosclerosis.

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