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.

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.

In replacement heifers, high levels of feeding resulting in high growth rates in the prepubertal period can cause severe reduction of the milk production potential. This has been demonstrated in many experiments; however, there are a number of experiments where this effect is not seen. In many cases, the reason for the lack of effect seems fairly obvious (short treatment periods, high pretreatment growth rates, small growth rate differences between treatment groups, variation of growth rates within treatment groups, treatment periods outside the critical period, etc.). However, in a few experiments absence of treatment effect cannot be explained in this way. This demonstrates that our knowledge on the effect of nutrition during rearing on the future milk yield of heifers is incomplete and that it may be possible to develop high growth rate feeding regimens for heifers. Experimental evidence suggests that the observed negative effects of feeding level on subsequent milk are due to impaired mammary development. Development of suitable high growth rate feeding regimens therefore requires understanding of the influence of nutrition on the physiological regulation of mammary development. Available data suggest that the growth hormone-insulin-like growth factor I axis is involved, but it is not clear how. It is likely that understanding of the role of insulin-like growth factor binding proteins is important. Alternative hypotheses involve possible effects of growth factors and modifications of mammary tissue sensitivity to hormones and growth factors. Copyright © . .