Camelina cake (CAM) is a co-product proposed as an alternative protein source; however, piglet data are still limited. This study aimed to evaluate the effect of different doses of CAM in substitution of soyabean meal on the growth, health and gut health of weaned pigs. At 14 d post-weaning (d0), sixty-four piglets were assigned either to a standard diet or to a diet with 4 %, 8 % or 12 % of CAM. Piglets were weighed weekly. At d7 and d28, faeces were collected for microbiota and polyamine and blood for reactive oxygen metabolites (ROM) and thyroxine analysis. At d28, pigs were slaughtered, organs were weighed, pH was recorded on gut, colon was analysed for volatile fatty acids (VFA) and jejunum was used for morphological and gene expression analysis. Data analysis was carried out using a mixed model including diet, pen and litter as factors; linear and quadratic contrasts were tested. CAM linearly reduced the average daily gain from d0–d7, d0–d14, d0–d21 and d0–d28 (P ≤ 0·01). From d0–d7 increasing CAM linearly decreased feed intake (P = 0·04) and increased linearly the feed to gain (P = 0·004). CAM increased linearly the liver weight (P < 0·0001) and affected the cadaverine (P < 0·001). The diet did not affect the ROM, thyroxine, intestinal pH, VFA and morphology. All doses of CAM increased the α diversity indices at d28 (P < 0·05). CAM at 4 % promoted the abundance of Butyricicoccaceae_UCG-008. Feeding with CAM enhanced resilience in the gut microbiome and can be evaluated as a potential alternative protein source with dose-dependent limitations on piglet growth performance.

The contribution of milk and dairy products to daily iodine intake is high but variable in many industrialised countries. Factors that affect iodine concentrations in milk and dairy products are only poorly understood. Our aim was to: (1) assess the effect of feed iodine concentration on milk iodine by supplementing five groups of five cows each with one of five dosages from 0–2 mg iodine/kg DM; (2) quantify iodine losses during manufacturing of cheese and yogurt from milk with varying iodine concentrations and assess the effect of cellar-ripening; and (3) systematically measure iodine partitioning during heat treatment and skimming of milk. Milk iodine reached a near-steady state after 3 weeks of feeding. Median milk iodine (17–302 μg/l for 0–2 mg iodine/kg DM) increased linearly with feed iodine (R2 0·96; P < 0·001). At curd separation, 75–84 % of iodine was lost in whey. Dairy iodine increased linearly with milk iodine (semi-hard cheese: R2 0·95; P < 0·001; fresh cheese and yogurt: R2 1·00; P < 0·001), and cellar-ripening had no effect. Heat treatment had no significant effect, whereas skimming increased (P < 0·001) milk iodine concentration by only 1–2 μg/l. Mean daily intake of dairy products by Swiss adults is estimated at 213 g, which would contribute 13–52 % of the adults’ RDA for iodine if cow feed is supplemented with 0·5–2 mg iodine/kg DM. Thus, modulation of feed iodine levels can help achieve desirable iodine concentrations in milk and dairy products, and thereby optimise their contribution to human iodine nutrition to avoid both deficiency and excess.

It is well known that severe iodine deficiency during pregnancy may cause impaired brain development in the child, with effects on cognitive and motor function, hearing and speech. Whether mild-to-moderate deficiency also affects neurological development is less well known, but in the past decade a number of observational studies have been conducted to answer this question and these studies are reviewed in this article. The picture is now emerging that even mild-to-moderate iodine deficiency during pregnancy may be associated with subtle impairments in cognition and school performance, although the evidence from randomised controlled trials is still lacking. As global efforts to eradicate iodine deficiency in populations continue, it is more likely that mild-to-moderate, rather than severe, iodine deficiency will be the issue of concern in pregnancy, and therefore further research in regions of mild-to-moderate deficiency is required to strengthen the research base and to inform public-health policy.

An experiment was conducted to determine: (1) the effect of excess maternal I supplementation on the thyroid hormone status of the ewe and her progeny; (2) potential mechanisms underpinning the failure of passive transfer associated with excess I and (3) the growing lambs’ response to natural gastrointestinal infection. Twin-bearing ewes received one of two treatments (n 32/treatment group): basal diet (C) or C plus 26·6 mg of iodine/ewe per d (I), supplied as calcium iodate. Ewes were individually fed from day 119 of gestation to parturition. Progeny of I ewes had lower (P<0·01) serum IgG concentrations from 24 h to 28 d postpartum but higher serum IgG concentrations at day 70 postpartum (P<0·05). I supplementation increased the relative expression of Fc receptor, IgA, IgM high affinity and polymeric Ig receptor in the ileum of the lamb at 24 h postpartum; however, thyroid hormone receptor-β (THRB) and β-2-microglobulin (B2M) expression declined (P<0·05). Progeny of I ewes had higher growth rates to weaning (P<0·05) and lower faecal egg count (FEC) for Nematodirus battus (P<0·05) between weeks 6 and 10 postpartum. In conclusion, excess maternal I supplementation negatively affected the thyroid hormone status, serum IgG concentration, ileal morphology and the gene expression of THRB and B2M in the ileum and ras-related protein (RAB) RAB25 and the mucin gene (MUC) MUC1 in the duodenum of the lamb postpartum. These effects were followed by an enhancement of average daily gain and lower N. battus FEC in the pre-weaning period of I-supplemented lambs.

The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21). In animal models linear growth is particularly sensitive to dietary protein as well as Zn intake, which act through insulin, insulin-like growth factor-1 (IGF-1) and its binding proteins, triiodothyronine, amino acids and Zn2+ to stimulate growth-plate protein and proteoglycan synthesis and cell cycle progression, actions which are blocked by corticosteroids and inflammatory cytokines. Observational human studies indicate stunting to be associated with nutritionally poor, mainly plant-based diets. Intervention studies provide some support for deficiencies of energy, protein, Zn and iodine and for multiple micronutrient deficiencies, at least during pregnancy. Of the animal-source foods, only milk has been specifically and repeatedly shown to exert an important influence on linear growth in both undernourished and well-nourished children. However, inflammation, caused by infections, environmental enteric dysfunction, which may be widespread in the absence of clean water, adequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity, in each case contributes to stunting, and may explain why nutritional interventions are often unsuccessful. Current interventions to reduce stunting are targeting WASH as well as nutrition.

Removing dietary phyto-oestrogens in adult male rats causes obesity and diabetes. As whey proteins have been reported to reduce food intake and improve glucose homoeostasis, we investigated whether they could attenuate susceptibility to obesity and diabetes due to phyto-oestrogen deprivation. To this end, thirty male Wistar rats were fed a high-phyto-oestrogen (HP) or a phyto-oestrogen-free (PF) diet for 10 weeks; six rats from each group were killed. The remaining HP animals (six animals) continued receiving the HP diet for 6 weeks. The remaining PF rats (twelve rats) were divided in two groups: one was given the PF diet and the other a variation of the PF diet plus whey protein (PF-W). Body weight, food intake and adipose tissue weights were recorded. Hypothalamic mRNA expressions of orexigenic (neuropeptide Y, agouti-related protein (AgRP)) and anorexigenic (pro-opiomelanocortin (POMC), cocaine-amphetamine-related transcript (CART)) neuropeptides were quantified by real-time PCR. Serum glucose, insulin and total thyroxine (T4), thyroid-stimulating hormone, testosterone and oestradiol were assessed. After 10 weeks of PF diet, increased body weight, adiposity and energy intake, with up-regulation of AgRP and down-regulation of POMC', were observed. Longer treatment exacerbated these results, increased total T4 levels, reduced oestradiol levels and impaired glucose homoeostasis. PF-W reduced energy intake and increased POMC expression; however, body weight and adiposity remained unchanged. PF-W could not prevent the hormonal changes or the high circulating glucose levels induced by phyto-oestrogen deprivation, but reduced fasting insulin. These data demonstrate that, although 6 weeks of whey administration could not prevent obesity in phyto-oestrogen-deprived rats, the reduction in energy intake and circulating insulin could be beneficial with longer treatments.

Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6–16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95 % CI 3·71, 6·89) nmol/l, stunted=6·62 (95 % CI 3·97, 11·02) nmol/l, underweight=2·51 (95 % CI 1·75, 3·63) nmol/l and recovered=3·46 (95 % CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95 % CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95 % CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95 % CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95 % CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95 % CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95 % CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95 % CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95 % CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95 % CI 1·18, 1·39) pmol/l, stunted=0·98 (95 % CI 0·87, 1·10) pmol/l, underweight=1·10 (95 % CI 1·01, 1·21) pmol/l and recovered=0·90 (95 % CI 0·83, 0·99) pmol/l (P<0·001). Multivariate analysis showed a lower cortisol concentration along 10 h (06.00–16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the recovered and control group. In conclusion, the children with recovery in weight and height had a cortisol stress response similar to control but a lower basal free T4. Longitudinal studies are warranted to determine the extent of these endocrine changes after recovery of undernutrition and in adulthood.

The objective of the present study was to assess the impact of providing small-quantity lipid-based nutrient supplements (SQ-LNS) on the I status of young Burkinabe children. In total, thirty-four communities were assigned to intervention (IC) or non-intervention cohorts (NIC). IC children were randomly assigned to receive 20 g lipid-based nutrient supplements (LNS)/d containing 90 µg I with 0 or 10 mg Zn from 9 to 18 months of age, and NIC children received no SQ-LNS. All the children were exposed to iodised salt through the national salt iodization programme. Spot urinary iodine (UI), thyroid-stimulating hormone (TSH) and total thyroxine (T4) in dried blood spots as well as plasma thyroglobulin (Tg) concentrations were assessed at 9 and 18 months of age among 123 IC and fifty-six NIC children. At baseline and at 18 months, UI, TSH and T4 did not differ between cohorts. Tg concentration was higher in the NIC v. IC at baseline, but this difference did not persist at 18 months of age. In both cohorts combined, the geometric mean of UI was 339·2 (95 % CI 298·6, 385·2) µg/l, TSH 0·8 (95 % CI 0·7, 0·8) mU/l, T4 118 (95 % CI 114, 122) nmol/l and Tg 26·0 (95 % CI 24·3, 27·7) µg/l at 18 months of age. None of the children had elevated TSH at 18 months of age. Marginally more children in NIC (8·9 %) had low T4 (<65 nmol/l) compared with the IC (1·6 %) (P=0·052). Salt samples (n 106) were collected from randomly selected participants and assessed by titration for I content, which was on average 37 (sd 15) ppm (range 5–86 ppm); 95 % of households had adequately iodised salt (I>15 ppm). A reduction of SQ-LNS I content could be considered in settings with similarly successful salt iodisation programmes.

To proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2 as well as of one-electron O2 reductants such as These two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of , and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2 and the O2 reductants when phosphorylating respiration fails to do this job due to lack of ADP.

In particular, it is proposed that some increase in the H+ leak of mitochondrial membrane in State 4 lowers , stimulates O2 consumption and decreases the level of which otherwise accumulates and serves as one-electron O2 reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.

Consumption of soya-based nutrients is increasing in modern society because of their potentially protective effects against chronic diseases. Soya products are also heavily advertised as alternative drugs for relief from symptoms of the menopause and for hormone replacement therapy.However, because of their oestrogenic activity, negative effects of isoflavones have been postulated. Therefore, we analysed influences of soya isoflavones, major soya constituents with endocrine activity, on thyroxine (T4) binding to its distribution proteins. Serum binding of 125I-labelled l-T4 was analysed in the absence or presence of increasing concentrations of soya isoflavones using non-denaturing PAGE for analysis. Complete displacement of [125I]T4 binding to transthyretin (TTR) was observed in human serum incubated with genistein at concentrations >10μm; interference started at >0·1μm. Glycitein showed decreased and daidzein the lowest displacement potency. [125I]T4 was displaced to albumin in rat and to T4-binding globulin in human serum. Soya isoflavones also obstruct [125I]T4 binding to TTR in human cerebrospinal fluid (CSF). The inhibitory effect was confirmed in direct binding assays using purified TTR with 50% inhibitory concentration values of 0·07μm for genistein, 0·2μm for glycitein and 1·8μm for daidzein. The present study underlined a potent competition of soya isoflavones for T4 binding to TTR in serum and CSF. Isoflavones might alter free thyroid hormone concentrations resulting in altered tissue availability and metabolism. As a consequence of this interference, one could expect a disturbance in the feedback regulation of hormonal networks, including the pituitary–thyroid–periphery axis during development and in adult organisms.

This paper reviews and presents data suggesting that the use of thyroxine (T4) to induce moult in poultry may be a viable alternative to previous methods involving feed withdrawal or feed avoidance. Studies completed in wild and domestic avian species have indicated that T4 is associated with the natural moulting process. Four experiments, spanning the range from using a purified, injectable form of T4 to a cost effective commercially available product, iodinated casein (economical source of T4) that can be fed to hens via a standard poultry ration, are presented. Since hens have full access to the diet during the induced moult, it is hoped that the procedure will be acceptable both to the poultry industry and to organizations concerned about the welfare of birds during this period of their annual cycle.

Numerous reports have concluded that zebrafish (Danio rerio) possesses A1-based visual pigments in their rod and cone photoreceptors. In the present study, we investigated the possibility that zebrafish have a paired visual pigment system. We measured the spectral absorption characteristics of photoreceptors from zebrafish maintained in different temperature regimes and those treated with exogenous thyroid hormone using CCD-based microspectrophotometry. Rods from fish housed at 15°C and 28°C were not significantly different, having λmax values of 503 ± 5 nm (n = 106) and 504 ± 6 nm (n = 88), respectively. Thyroid hormone treatment (held at 28°C), however, significantly shifted the λmax of rods from 503 ± 5 nm (n = 194) to 527 ± 8 nm (n = 212). Cone photoreceptors in fish housed at 28°C (without thyroid hormone treatment) had λmax values of 361 ± 3 nm (n = 2) for ultraviolet-, 411 ± 5 nm (n = 18) for short-, 482 ± 6 nm (n = 9) for medium-, and 565 ± 10 nm (n = 14) for long-wavelength sensitive cones. Thyroid hormone treatment of fish held at 28°C significantly shifted the λmax of long-wavelength sensitive cones to 613 ± 11 nm (n = 20), substantially beyond that of the λmax of the longest possible A1-based visual pigment (∼580 nm). Thyroid hormone treatment produced smaller shifts of λmax in other cone types and increased the half-band width. All shifts in photoreceptor λmax values resulting from thyroid hormone treatment matched predictions for an A1- to A2-based visual pigment system. We therefore conclude that zebrafish possess a rhodopsin–porphyropsin interchange system that functions to spectrally tune rod and cone photoreceptors. We believe that these observations should be carefully considered during analysis of zebrafish spectral sensitivity.

Transthyretin (TTR) is a transport protein for thyroid hormones and vitamin A and might have an important role in the nervous system. However, TTR can undergo a conformational change and form amyloid fibrils, in both acquired and hereditary forms of systemic amyloidosis. More than 80 TTR mutations have been associated with autosomal dominant amyloidosis, usually presenting with peripheral and autonomic neuropathy and/or cardiomyopathy. Major areas of research in TTR amyloidosis include: molecular mechanisms leading to fibril formation; mechanisms of fibril-induced cell death; modulators of phenotypic expression of the disease; and therapeutic strategies.

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3′,5′,3,5-L-tetraiodothyronine (T4), 3′,5,3-L-triiodothyronine (T3), 3′,5′,3-L-triiodothyronine (rT3) and 3,5,-L-diiodothyronine (3,5-T2). At physiological pH, dissociation of the phenolic −OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distribution throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones have many effects in vertebrates. It is proposed that there are several modes of action of these hormones. (1) The nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidification. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellular matrix. The effects of thyroid hormones are reviewed and appear to be combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re-examination of data from the early 1960s supports a membrane action. Findings from receptor ‘knockout’ mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as ‘vitamone’-like molecules than traditional hormonal messengers.

Mice infected with Toxoplasma gondii manifest a rapid decline in serum thyroxine (T4) levels. To locate the locus of the hypothyroxinaemia, the integrity of the pituitary–thyroid axis of infected mice was assessed by a thyrotropin-releasing hormone (TRH) assay. A rise in serum T4 after inoculation of TRH implies the release of thyrotropin (thyroid-stimulating hormone) from a functionally intact pituitary. Administration of a single, large-dose (1 μg) bolus of TRH to infected mice induced a positive, although subnormal, T4 response. In contrast, when infected mice were pre-treated with a series of low-dose (5 ng) pulses of TRH prior to the bolus challenge, the T4 response was markedly enhanced. We suggest that the multiple inoculations of low-dose pulses of TRH ‘primed’ the pituitary (and secondarily the thyroid) and led to replenishment of their readily available hormone reserves and the heightened response to stimulation. These observations indicate that the locus of thyroid dysfunction is in the hypothalamus, not the pituitary or thyroid, and apparently involves impairment of the pulsatile release of TRH.