Iodine, through the thyroid hormones, is required for the development of the auditory cortex and cochlea (the sensory organ for hearing). Deafness is a well-documented feature of endemic cretinism resulting from severe iodine deficiency. However, the range of effects of suboptimal iodine intake during auditory development on the hearing ability of children is less clear. We therefore aimed to systematically review the evidence for the association between iodine exposure (i.e. intake/status/supplementation) during development (i.e. pregnancy and/or childhood) and hearing outcomes in children. We searched PubMed and Embase and identified 330 studies, of which thirteen were included in this review. Only three of the thirteen studies were of low risk of bias or of good quality, this therefore limited our ability to draw firm conclusions. Nine of the studies (69 %) were in children (one RCT, two non-RCT interventions and six cross-sectional studies) and four (31 %) were in pregnant women (one RCT, one cohort study and two case reports). The RCT of iodine supplementation in mildly iodine-deficient pregnant women found no effect on offspring hearing thresholds. However, hearing was a secondary outcome of the trial and not all women were from an iodine-deficient area. Iodine supplementation of severely iodine-deficient children (in both non-RCT interventions) resulted in improved hearing thresholds. Five of six cross-sectional studies (83 %) found that higher iodine status in children was associated with better hearing. The current evidence base for the association between iodine status and hearing outcomes is limited and further good-quality research on this topic is needed.

Micronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS’s components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

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.

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.

Patients undergoing the modified Fontan procedure may develop low cardiac output postoperatively. Since thyroid hormone has important effects on cardiovascular function, the present study was undertaken to evaluate the influence of triiodothyronine supplementation. Ten consecutive patients under-going the Fontan procedure were administered intravenous triiodothyronine (0.4 mcg per kg) following surgery. Clinical outcome and thyroid hormone profiles were assessed and then compared to a previous series of patients undergoing the Fontan procedure who had not received triiodothyronine supplementation. Both groups initially demonstrated marked decreases in serum free triiodothyronine levels. The group which received triiodothyronine supplementation demonstrated a more rapid return of serum triiodothyronine levels to baseline [259±17 vs 121±15 pg/dl (p<0.05) on the fifth postoperative day and 336±18 vs 178±12 pg/dl (p<0.05) on the eighth day]. In addition, patients receiving supplemental triiodothyronine demonstrated more rapid recovery of total triiodothyronine, free thyroxine, total thyroxine and thyroglobulin levels. The group which received triiodothyronine supplementation had a shorter length of hospital stay [9±2 vs 14±3 (p<0.05)] as compared to patients who did not receive exogenous triiodothyronine. The results of this study demonstrate that triiodothyronine supplementation aids in the recovery of thyroid hormone levels following Fontan procedure. This endocrinologic finding correlated with improved clinical outcome.

Objective: Thyroid hormone has important effects on cardiovascular performance. This study was performed to evaluate the changes in levels of triiodothyronine following the first stage of reconstruction for hypoplastic left heart syndrome. Methods: We enrolled 14 newborns with hypoplastic left heart syndrome scheduled for first stage reconstruction. Blood samples were obtained pre-, intra-, and post-operatively. Levels of free and total triiodothyronine were determined by radioimmunoassay. Statistical comparison was performed using Wilcoxon's signed rank test. Results: The levels of free triiodothyronine decreased from a baseline of 355 ± 31 pg/dl to 205 ± 21 pg/dl upon the institution of bypass, and declined to a level of 135 ± 9 pg/dl at 24 hours postoperatively. Similarly, levels of total triiodothyronine decreased from 101 ± 15 ng/dl to 65 ± 4 ng/dl upon the institution of bypass, and continued to decline during the first 24 hours postoperatively. Levels of free and total triiodothyronine had returned to baseline by the fifth postoperative day. Conclusions: The data demonstrate significant decreases in levels of free and total triiodothyronine during the early postoperative period. These changes in levels of thyroid hormone may have adverse effects on cardiac function during this phase of recovery.

The changes in metabolic efficiency, body composition, and nutrient partitioning induced by high-fat feeding were evaluated in adult rats (90d of age). The alterations in serum free triiodothyronine, insulin, and leptin levels, as well as in hepatic and skeletal muscle metabolism, were also assessed. Rats were fed either a low- or a high-fat diet for 2 weeks. Relative to the low-fat feeding, energy intake and expenditure, as well as body-energy gain, lipid gain, and energetic efficiency, were increased by the high-fat feeding. Increased serum leptin levels accompanied these variations. A positive correlation between serum leptin levels and percentage of body fat was found in the rats fed the low- or high-fat diet, with a significant divergence between the slope of the regression lines. Furthermore, a negative correlation between serum leptin level and energy intake was found in the rats fed the low-fat diet, while a positive correlation was found in the rats fed the high-fat diet. Finally, the high-fat feeding decreased the hepatic and skeletal muscle mitochondrial oxidative capacity. It is concluded that, in adult rats, a nutritional factor such as a high level of fat in the diet induces obesity, leptin resistance, and impairment of mitochondrial capacity, all phenomena typical of unrestrained aged rats.

Variations in energy balance, body composition, and nutrient partitioning induced by high-fat feeding, cold exposure or by concomitant high-fat feeding and cold exposure were studied in young Wistar rats. Changes in hepatic metabolism as well as in serum free triiodothyronine and leptin levels were also evaluated. Rats were exposed to either 24 or 4°C and fed either a low- or high-fat diet (10 % or 50 % energy respectively) for 2 weeks. Relative to low-fat feeding at 24°C, both energy intake and expenditure were increased by high-fat feeding or by cold exposure, and these changes were accompanied by increased serum triiodothyronine levels. In response to concomitant high-fat feeding and cold exposure, serum triiodothyronine tended to be further elevated, but no further increases in energy intake or energy expenditure were observed. Independently of diet, the increased energy expenditure in cold-exposed rats was not completely balanced by adaptive hyperphagia, with consequential reductions in protein and fat gain, accompanied by marked decreases in serum leptin. Furthermore, unlike high-fat feeding at 24°C, cold exposure enhanced hepatic mitochondrial oxidative capacity both in the low-fat- and high-fat-fed groups. It is concluded that in this strain of young Wistar rats, despite similarly marked stimulation of energy expenditure by high-fat feeding at 24°C, by cold exposure and by concomitant high-fat feeding and cold exposure, an increased hepatic oxidative capacity occurred only in the presence of the cold stimulus.

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.

Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing either 120 or 210 g crude protein and 0 or 1 mg triiodothyronine (T3)/kg diet to study in vitro lipogenesis (IVL). In addition, a carry-over period (180 g crude protein/kg diet from 28 to 40 d of age) was used to test the persistence of prior treatment effects. The higher protein level increased, but T3 decreased (P < 0.01) growth and feed consumption at 28 d of age. The lower protein level increased (P < 0.05) and T3 decreased IVL in 28-d-old chickens. These effects were only sustained for 6 d following the switch to a common diet at 28 d. IVL at 40 d of age was not affected by either crude protein or T3 fed during the 7–28 d period. The higher protein level increased plasma insulin-like growth factor-1 during the period from 7 to 28 d; however, this effect lasted for only 6 d following the switch to a common diet. Plasma growth hormone (GH) at 28 d of age was inversely related to dietary protein level. Changing to a common level of crude protein did not change plasma GH values at 12 d, indicating that the nutritional state of the young chicken may affect GH at a later period of life. Metabolic changes noted in this study were rapid and maintained for a short period of time following the feeding of a common diet.

Lipogenesis: Dietary protein: Triiodothyronine

Indian River male broiler chickens growing from 7 to 30 d of age were fed on diets containing crude protein levels ranging from 120 to 3041 g/kg plus 0 or 1 mg triiodothyronine (T3/)kg diet. The purpose of this study was to examine the effects of these treatments on lipogenesis after a common diet was fed (180 g crude protein/kg diet from 30 to 56 d of age). Dietary treatment groups were sampled at 30 and 56 d. In vitro lipogenesis was determined by incubating liver explants for 2h at 37°in Hanks' salts containing 25 mM-HEPES and 10 mM-[2-14C]acetate and then measuring acetate incorporation into total lipid. Growth and feedconsumption from 7 to 30 d increased (P<0·01) as dietary protein increased from 120 to 210 g/kg diet. Both measurements decreased as crude protein increased from 210 to 300 g/kg diet.T, decreased (P<0·01) growth and feed intake during this period.Low-protein (<180 g/kg) diets increased (P<0·05) and T3, decreased lipogenesis in 30-d-old chickens. Although birds given T3from 7 to 30 dgrew at the greatest rate from 30 to 56 d of age, the final body weight was still less than controls.In vifm lipogenesis at 56 d of age was not affected by either of the two dietary treatments. In contrast, the relative size of the abdominal fat pad (g/kg body weight) at 56 d was decreased by feeding T3from 7 to 30 d. Any changes in metabolism elicited by either dietary protein levels or hormone treatments may be specific to the particular dosing interval and are not sustained when acommon diet is fed during a repletion period.

The effect of melatonin implants administered to cashmere goats in the winter, on plasma prolactin, triiodothyronine (T3) and thyroxine (T4) concentrations and the timing of the spring moult, was studied with the objective of identifying a method of manipulating the timing of the spring moult and increasing fibre harvesting efficiency. The effect of similar melatonin implants on prolactin concentration when administered in the increasing daylength of spring, was also measured.

In the first experiment, using 20 juvenile and 20 adult female cashmere goats, half the animals of each group received continuous release implants of melatonin (18 mg) on 11 December, 1 February and 1 April. In the adult goats the treatment significantly advanced by 7 weeks the time at which peak plasma prolactin concentrations were attained (P < 0·001) and advanced the onset (P < 0·001) of the peak. The treatment also resulted in an advance of the spring moult of cashmere in the adult goats (P < 0·01) and in an earlier initiation (P < 0·01) of the growth of both guard hair and cashmere as judged by histological examination of primary and secondary hair follicles. In the juvenile goats there were no significant effects of melatonin administration on plasma prolactin concentrations, the timing of the moult, or on any of the histological measurements compared with the controls. There were no significant effects on live weight or circulating concentrations of T3 and T4 in either age group. In the second experiment, the administration of one melatonin implant (18 mg) to three adult goats on 1 April caused a significant reduction in plasma prolactin concentrations (P < 0·05) over a period of 3 weeks compared with concentrations observed in four untreated goats.

It is concluded that treatment with melatonin implants is effective in modifying the timing of the seasonal cycle in prolactin secretion in adult cashmere goats and causing corresponding changes in hair follicle activity. However, since the treatment initiated in December caused an advance rather than a delay in the normal spring rise in plasma prolactin concentrations, it is evident that the repeated melatonin implant protocol used in this experiment cannot be used to delay the onset of the spring moult and thus facilitate the harvesting of cashmere.

Indian River male broiler chickens (7-d-old) were fed on diets containing 120, 210 or 300 g crude protein/kg + 0 or 1 mg triiodothyronine (T3)/kg diet (Expt 1) and 120, 150, 180 or 210 g crude protein/kg +0 or 1 mg T3/kg diet (Expt 2) to determine the effects of crude protein level and T3 on growth and metabolism. Body composition of chickens was determined by a combination of dissection of muscle and abdominal fat pads, and chemical extraction (Expt 1). In vitro lipogenesis (IVL) was determined in both experiments by incubating liver explants for 2 h at 37° in the presence of 10-4 M-dibutyryl cyclic AMP (cAMP) or 10-5 M isoproterenol (ISO) and 10-2 M-[2-14C]acetate. Acetate incorporation into total lipid was an indication of IVL. Activity ratios for each of these additions relative to control (?cAMP?ISO) were calculated to ascertain basal ν. inhibited rates of IVL. The relative muscle mass was increased by increasing crude protein from 120 to 210 g/kg diet but not from 210 to 300 g/kg diet. Dietary T3 decreased total body lipid regardless of the dietary crude-protein level. Increasing dietary crude protein decreased (P<0.05) basal IVL (?cAMP? ISO) but not IVL (+ cAMP). Dietary T3 decreased basal IVL in birds fed on the diets containing 120 and 210 g crude protein/kg but had little effect on the two inhibited states of lipogenesis (+ cAMP or +ISO). The component of lipogenesis sensitive to in vitro inhibition is also the component under dietary control.

This study was conducted to determine the relationship between plasma concentrations of thyroxine (T4), triiodothyronine (T3) and body weight in young Majaheem male camels. Eighteen camels aged 6 to 7 months were divided equally into three groups (Gl, G2 and G3). All groups were given concentrate pellets (187 g crude protein per kg) at the rate of 15 g/kg body weight daily. In addition, each group was given one of the following roughages: lucerne hay to Gl, rhodes grass hay to G2 and ammonia-treated wheat straw to G3. Roughages, salt and water were measured and given ad libitum. Every 2 weeks all camels were weighed and blood samples were collected. Data were statistically analysed using a general linear model procedure. There was a positive correlation between T4 concentration and body weight. T4 was higher in camels given either hay or straw compared with those given rhodes grass hay, while there were no differences among the three groups in T3 and in body weight.