Determinants of the annual pattern of reproduction in mature male Merino and Suffolk sheep: responses to a nutritional stimulus in the breeding and non-breeding seasons

This study was designed to test whether an acute improvement in diet would increase gonadotrophin secretion and testicular growth in strongly photoperiod-responsive Suffolk rams and weakly photoperiod-responsive Merino rams in both the breeding (February-March) and the non-breeding (July-August) seasons. Mature rams (n = 5 or 6) of these breeds were fed a maintenance diet (0.9 kg chaff + 100 g lupin grain) or the same diet supplemented with 1.5 kg lupin grain for 42 days in each season. Lupin grain is a rich source of both energy and protein. Testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured in plasma from blood sampled every 20 min for 24 h on Days -1, 12 and 35 relative to the change in feeding. In rams supplemented with lupins, body mass increased in both breeds in both seasons (P < 0.001). Scrotal circumference and LH pulse frequency increased with lupin supplementation in both seasons (P < 0.003) in Merinos, but only during the breeding season (P < 0.003) in Suffolks. Plasma FSH concentrations were affected by diet only during the breeding season, being elevated on Day 12 in lupin-supplemented rams of both breeds (P < 0.05). It was concluded that Merino rams exhibit reproductive responses to improved nutrition irrespective of time of the year, whereas Suffolk rams respond to nutrition only when the hypothalamic reproductive centres are not inhibited by photoperiod. Thus, Suffolks do respond to nutrition, just as Merinos do, but only when photoperiod allows. This difference between breeds appears to be a result of differences in the neuroendocrine pathways that control pulsatile gonadotrophin-releasing hormone secretion.     

Effect of dietary intake on steroid feedback on release of luteinizing hormone in ovariectomized cows

This study tested the hypothesis that the decline in pulsatile release of luteinizing hormone (LH), resulting from steroid negative feedback, is greater in animals fed a low, compared with a high, plane of nutrition. Two-year-old cows were ovariectomized and six days later were fed diets to provide 1.5 x maintenance requirements (n = 6, supplemented) or 0.5 x maintenance requirements (n = 6, restricted) (Round 1). Pulsatile release of LH was measured over a 14-h period on the fifth day of feeding these diets (Day 1); at 6 h, all animals were treated with an intravaginal insert containing 1.38 g progesterone, which remained in place until the end of Day 3. Pulsatile release of LH was again measured for 14 h on Day 3; at 6 h, all animals were injected intramuscularly with oestradiol benzoate (ODB; 1 mg per 500 kg live weight). Three days later, this protocol was repeated, in a cross-over design, with cows that were previously restricted now being supplemented and those cows previously supplemented, now restricted (Round 2). Plasma concentrations of progesterone after intravaginal progesterone treatment were 1.01 ng mL(-1) higher in restricted cows compared with supplemented cows (P < 0.001) and were also higher in Round 1 than in Round 2 and on Day 1 than on Day 3 (P < 0.001). Plasma concentrations of oestradiol following injection with ODB did not differ between supplemented and restricted cows (P > 0.1). Dietary intake did not affect mean concentrations of LH, pulse frequency or amplitude during the 6-h period before steroid treatment or the change in these variables following steroid treatment; however, the slope of the decline in concentrations of LH following progesterone treatment was significantly more negative in cows fed restricted diets compared with those fed supplemented diets. In Round 2, mean concentrations of LH were higher preceding, and decreased more following, progesterone treatment compared with the decrease after ODB treatment. In conclusion, acute dietary restriction resulted in a more rapid decline in the release of LH following treatment with intravaginal progesterone, and was associated with higher concentrations of progesterone in plasma.     

Reproduction and plasma concentrations of leptin,insulin and insulin-like growth factor 1 in growth-hormone-transgenic female sheep before and after artificial insemination

The transgenic sheep used in this study expressed an additional copy of the gene for ovine growth hormone (GH), so they had continuously high plasma concentrations of GH. They were used to test whether the GH transgene affected plasma concentrations of the metabolic hormones leptin, insulin-like growth factor 1 (IGF-1) and insulin, and whether these effects were associated with changes in conception, pregnancy or parturition following artificial insemination. Compared with control animals, the GH-transgenic sheep had higher bodyweight, lower body condition score and less subcutaneous fat (P < 0.05). These sheep also had lower plasma concentrations of leptin, higher plasma concentrations of insulin, and higher plasma concentrations of IGF-1 (P < 0.001). A similar proportion of GH-transgenic and control ewes came into oestrus, but the conception rate to artificial insemination was lower in GH-transgenic ewes than in the controls. Only four live lambs were recovered from 12 GH-transgenic ewes (33%) compared with 38 lambs from 43 controls (88%). This outcome was not associated with any difference in plasma progesterone profile in the period leading up to artificial insemination (Day 0). The GH-transgenic ewes had lower concentrations of FSH at all times measured (Day -19, Day -2 and Day 19). These results indicate that appropriate regulation of GH secretion from pituitary or peripheral tissues is necessary for normal reproduction and normal levels of metabolic hormones. Chronically high concentrations of GH were associated with increased levels of IGF-1 and insulin, and decreased levels of leptin.     

Gene expressions of leptin, insulin receptors and lipogenic enzymes are coordinately regulated by insulin and dietary fat in rats

Regulation of the gene expressions of leptin, insulin receptors and lipogenic enzymes was investigated after refeeding a fat-free diet or a 10 g/100 g corn oil diet to food-deprived rats. Plasma glucose and insulin concentrations began to increase 30 min after the feeding and further increased up until 8 h. In these rats, the expression of leptin mRNA in adipose tissue began to increase significantly only 30 min after feeding, and reached a maximum at 8-16 h. However, plasma leptin levels did not increase until 4 h after refeeding, then markedly increased and reached the maximal level after 8 h. The expression of leptin mRNA and plasma leptin concentrations generally were greater in rats fed the corn oil diet compared to those fed the fat-free diet. Insulin receptor mRNA concentrations in the liver and adipose tissue began to decrease 30 min after the refeeding, in contrast to the plasma insulin increase, and continued to decrease until 8 h. The expression of acetyl-CoA carboxylase and fatty acid synthase mRNA began to increase 4-8 h after feeding and reached maximal levels at 16-24 h. Leptin treatment suppressed the expression of lipogenic enzyme mRNA in rats fed the fat-free diet but not in corn oil-fed rats, in which the expression was suppressed by polyunsaturated fatty acids and leptin expression was higher. Thus, we suggest that the glucose and insulin-dependent expressions of leptin, insulin receptors and lipogenic enzymes are coordinately and/or mutually regulated by dietary manipulation.     

Plasma leptin is regulated predominantly by nutrition in preruminant lambs

In juvenile and mature animals, the plasma concentration of leptin is regulated by adiposity and nutrition. However, the timing of these influences on plasma leptin, and their relative importance in early postnatal life, are unknown. We investigated these plasma leptin influences in sheep, a species characterized during fetal life by leanness and insensitivity of leptin to variation in maternal nutrition. Small and large neonatal lambs were randomly assigned to either a diet sustaining an average daily weight gain (ADG) of 148 g/d (Low plane) or ate ad libitum a diet sustaining an ADG of 337 g/d (High plane). A subset of animals were slaughtered at 7.5, 10, 15 and 20 kg of body weight. Birth size had no effect on plasma leptin concentrations and adiposity at birth or at later times. Plasma leptin concentrations increased within 6 d of birth in the High plane lambs (P < 0.01) and continued to rise over time. In contrast, plasma leptin concentrations never changed in the Low plane lambs despite increasing adiposity. The positive association between plasma leptin concentration and adiposity was greater in the High plane than in the Low plane lambs, suggesting an independent effect of nutrition. Consistent with this finding, lipid accretion rates, a variable that is mostly independent of adiposity, was a strong predictor of plasma leptin concentrations only in the High plane lambs (R(2) = 0.77, P < 0.01). A positive association between plasma insulin and leptin developed over time in the High plane lambs (R(2) = 0.75, P < 0.01 on d 40), but was not seen in the Low plane lambs. These data indicate that both nutrition and adiposity regulate plasma leptin synthesis in early postnatal life, but in contrast to adulthood, the effects of nutrition appear to be predominant.     

Early nutrition and leptin concentrations in later life

BACKGROUND: Formula feeding or overweight in infancy may increase the later risk of obesity, but the mechanisms involved are uncertain. Because obesity is associated with high leptin concentrations relative to fat mass, programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity. OBJECTIVE: We tested the hypothesis that high nutrient intake or formula feeding in infancy programs greater leptin concentrations relative to fat mass in later life. DESIGN: Serum leptin concentrations were measured by radioimmunoassay in 197 adolescents aged 13-16 y who were born preterm and randomly assigned at birth to receive either a nutrient-enriched preterm formula or banked donated breast milk (trial 1) or a preterm formula or a standard formula (trial 2). Fat mass was estimated with the use of bioelectrical impedance analysis. RESULTS: After combining the results of trials 1 and 2 as planned, the ratio of leptin to fat mass was significantly greater in the children who received the preterm formula (geometric : 0.84 microg x L(-1) x kg(-1)) than in those who received standard formula or banked breast milk (0.62 microg x L(-1) x kg(-1); mean difference: 30.8%; 95% CI for difference: 8.4%, 53.2%; P = 0.007). The difference between the diet groups remained significant after adjustment for age, sex, Tanner stage, social class, and fat mass. Human milk intake was significantly associated with lower leptin concentrations relative to fat mass in adolescence (P = 0.023), independent of potential confounding factors. CONCLUSION: Programming of relative leptin concentrations by early diet may be one mechanism that links early nutrition with later obesity.     

13岁儿童肥胖发生相关因子与青春期发育相关激素分泌及其关系研究

目的分析儿童肥胖形成中肥胖发生调节因子及与青春期发育相关激素的变化,探讨这些激素在青春期儿童肥胖形成中的变化特点及其相互关系。方法以78例肥胖的13岁儿童和84例同岁正常对照儿童为研究对象,以放射免疫法测定血中食欲素(orexins)、瘦素(leptin)、胰岛素(insulin)及睾酮(T)、雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)等浓度,计算骨龄(BA)。结果肥胖儿童血中leptin、insulin浓度显著高于对照组浓度(P<0·01);肥胖儿童血中OrexinA浓度显著低于对照组浓度(P<0·01);肥胖男生T浓度显著低于对照组,肥胖女生E2、LH浓度显著高于对照组(P<0·01);男女肥胖儿童骨龄明显大于对照组,且随着骨龄的增大血中leptin,LH含量明显增加;男女肥胖与正常儿童LH与FSH之间、leptin与insulin,C-肽,E2之间均存在正相关关系(P<0·01);对照组男生LH、FSH与E2存在正相关关系(r=0·373、0·314,P<0·05);leptin与T存在负相关关系(r=-0·423)P<0·01,与FSH存在正相关关系(r=0·308,P<0·05);对照组女生leptin、LH与E2均存在正相关性(r=0·585、0·647,P<0·01);男女肥胖组LH、FSH与T,E2之间均未发现相关关系,肥胖男生leptin与T呈负相关关系(r=-0·574,P<0·01)。结论肥胖儿童相对与正常儿童血中leptin,orexina,insulin和T,E2,LH浓度发生了明显变化,肥胖儿童高浓度leptin水平可使体内T,E2,LH浓度水平发生变化,影响肥胖儿童的青春期发育。     

Role of peripheral and central aromatization in the control of gonadotrophin secretion in the male sheep

Both testosterone and its aromatized metabolite, oestradiol-17beta, are known to act centrally on the secretion of GnRH, but the major site of aromatization is not clear as aromatase activities are found in numerous tissues including brain and testis. Here, we tested the importance of central aromatization of testosterone using a non-steroidal aromatase inhibitor, fadrozole. To distinguish between testicular and non-testicular sites, five intact and five testosterone-infused castrated rams (600 microg kg(-1) per 24 h for 3 days) were given four injections of fadrozole (i.m.; 500 microg kg(-1)) at 48, 52, 64 and 68 h relative to the start of testosterone infusion. Control rams (n = 5) received vehicle only. Fadrozole treatment decreased plasma oestradiol-17beta concentrations and increased the LH pulse frequency in both intact rams and testosterone-treated castrates, suggesting that non-testicular sites of aromatization are important in the control of pulsatile LH secretion. To test the importance of central aromatization, intact rams (n = 5) were infused into the third ventricle with vehicle (artificial cerebrospinal fluid) or with fadrozole (20 and 200 microg kg(-1) per day). After two weeks, the same two doses of fadrozole were infused intravenously instead of intracerebrally. Central infusion of fadrozole did not affect plasma oestradiol concentrations but increased LH pulse frequency. Only the highest dose increased LH pulse frequency when infused intravenously. In conclusion, central aromatization is involved in the control of pulsatile LH secretion in male sheep.     

Effects of a preovulatory administered depot gonadotrophin-releasing hormone agonist on reproductive hormone levels and pregnancy outcome in gilts

The present study aimed to explore the influence of a preovulatory administered depot gonadotrophin-releasing hormone (GnRH) agonist (GnRHa; Decapeptyl Depot) on the endocrine parameters and pregnancy outcome of gilts (n = 6). A GnRHa-supported preovulatory luteinising hormone (LH) surge was detected in all treated gilts. LH pulses were abolished completely by depot GnRHa on Day 7 and partly on Day 21 of pregnancy. In this treatment group (n = 6) four gilts were pregnant at slaughter on Day 28. In the control group receiving Gonavet, a non-formulated GnRHa (n = 6), all pigs showed LH pulses and were pregnant at slaughter on Day 28 of gestation. Mean progesterone concentrations were elevated in controls during the early luteal phase and were similar for both groups during the implantation period. Mean concentration of unoccupied progesterone receptor was significantly higher in uterine myometrium than in endometrium, but without treatment effects. Peripheral estrone sulfate concentrations showed a similar increase in all pregnant gilts on Days 17 and 18, and remained elevated. In summary, treatment with a depot GnRHa for synchronisation of ovulation alters pulsatile LH secretion during early pregnancy in pigs. In general, this alteration seems not to exert an injurious influence on luteal function and, therefore, on embryo and early fetal development.     

Pulsatile release of luteinising hormone during the luteal phase in lactating and weaned sows

The present paper describes luteal phase luteinising hormone (LH) in sows that ovulated due to a limited nursing regimen (LN). The LN regimen was imposed either at Day 14 or at Day 21 of lactation. At ovulation, lactation was terminated (n = 8) or sows remained lactating throughout early pregnancy (n = 8). Blood samples were collected every 15 min for 8 h during the day, around Day 11 after ovulation. In addition, lactating sows were bled during the night, when piglets were allowed to suckle. The LH pattern was typical for the luteal phase, with one to five pulses per 8 h. The LH characteristics (frequency, base, average, pulse area) did not differ between lactating and weaned sows, except for the amplitude of LH pulses, which was higher in weaned sows compared with lactating sows (1.22 +/- 0.15 v. 0.76 +/- 0.11 ng mL(-1), respectively; P < 0.05). In lactating sows, average LH, basal LH and the frequency of LH pulses were significantly lower during the night, when piglets were allowed to suckle. The sage of lactation at which LN was imposed did not influence LH. In conclusion, it is unlikely that the small difference in LH explains the considerable difference between lactating and weaned sows in progesterone at Day 12 of pregnancy (24.1 +/- 1.3 v. 43.3 +/- 4.0 ng mL(-1), respectively; P < 0.01). Moreover, the difference in progesterone already exists during the early luteal phase (Day 0-10), when secretion of the corpora lutea is still independent of LH.     

Influence of surgical stress and parenteral nutrition on serum leptin concentration

Experimental studies suggest that leptin may be an important metabolic signal for energy regulation. AIM: To assess whether surgical stress produces changes in serum leptin concentration and to investigate and compare the effect of total parenteral nutrition and hypocaloric parenteral nutrition on serum leptin levels. PATIENTS AND METHODS: Twenty-two surgical patients (11 male and 11 female) in need of parenteral nutrition were recruited. Parenteral nutrition was always initiated 24 h after surgical procedure. Group I (n=15) received total parenteral nutrition, while Group II (n=7) were treated with hypocaloric parenteral nutrition. Serum leptin concentration was determined before surgical procedure (day -1), after surgery and before parenteral nutrition was started (day +1), and after 5 days of treatment with parenteral nutrition (day +6). RESULTS: A tendency to increase serum leptin levels was observed after surgical procedure (6.0+/-1.9 vs 9.9+/-2.7 ng/ml;P= 0.07). After starting parenteral nutrition no significant changes on serum leptin concentrations were found in both groups, but a trend to raise serum leptin was observed in Group I (6.2+/-1.7 vs 8.3+/-2.7 ng/ml) whereas a trend to decrease serum leptin was detected in Group II (4.6+/-2.5 vs 1.6+/-0.5 ng/ml). On day +6 an increase of serum leptin and insulin levels was observed in Group I in comparison with Group II (8.3+/-2.7 vs 1.6+/-0.5 ng/ml;P< 0.05 and 58+/-41 vs 12+/-15 microU/l;P< 0.05 respectively). Finally, a positive correlation at day +6 between insulin and serum leptin levels was observed (r= 0.66;P< 0.01). CONCLUSIONS: a) Surgical stress is associated to an increase of serum leptin concentrations; b) Total and hypocaloric parenteral nutrition produces quite different effects on serum leptin levels that could be related to distinct insulin response.     

Feeding frequency for lactating cows: diurnal patterns of hormones and metabolites in peripheral blood in relation to milk-fat concentration

1. The present paper reports the effects of dietary modifications on the diurnal pattern of concentrations of certain metabolites and hormones in the peripheral blood of lactating dairy cows. The cows were given fixed rations of hay and high-cereal concentrates in the proportions of 30:70 or 10:90 (w/w). The concentrates were given in either two or six equal meals daily; the hay was given twice daily. 2. Previous reports of the same experiment had shown that milk-fat yield and concentration were reduced by increasing the proportion of concentrates in the diet and increased by more frequent feeding of the concentrates. These changes could be explained in part by changes in rumen volatile fatty acid (VFA) proportions and mean daily concentrations of VFA, particularly propionic acid, and insulin in the peripheral blood, but these factors failed to explain all the increase in milk-fat concentration caused by more frequent feeding. 3. Analysis of blood samples taken at hourly intervals for 24 h at two stages of lactation showed that, in the cows fed six times daily, the concentrations of metabolites and hormones remained relatively constant over the day. In the cows fed twice daily, the concentrations of VFA, 3-hydroxybutyric acid and insulin all increased after both meals whereas the concentrations of glucose and growth hormone tended to fall. The concentration of non-esterified fatty acids tended to increase overnight and fall rapidly after the morning feed. The concentrations of glucagon, thyroxine and prolactin showed no clear pattern in relation to meals. The postprandial responses of propionate, insulin and growth hormone were greater with the higher concentrate diet. 4. The maximum concentration and the diurnal range of concentrations were reduced by more frequent feeding of both diets in the case of propionic acid and of the higher concentrate diet in the case of insulin, but the effects on insulin concentrations of more frequent feeding of the lower concentrate diet were smaller and not significant. The maximum concentration and the diurnal range of concentrations of growth hormone were unaffected by meal frequency. 5. It is concluded that the severity of milk-fat depression in cows fed twice daily is increased by the rapid rise in propionic acid concentration in the peripheral blood after a meal, which in turn increases insulin secretion and may be accompanied by a suppression of growth hormone release. This causes lipogenesis to be diverted towards adipose tissue at the expense of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)     

The human body may buffer small differences in meal size and timing during a 24-h wake period provided energy balance is maintained

Because approximately 20% of the work force in the industrialized world have irregular working hours, it is pertinent to study the consequences of eating at irregular, especially nighttime hours. We studied the postprandial responses during nocturnal fasting vs. eating throughout a 24-h wake period. Seven healthy males were studied twice in a crossover design. After a 6-d diet adjustment period [high fat diet, 45 energy percent (en%) fat, 40 en% carbohydrates)] with sleep from 2300 to 0700 h, the men were kept awake for 24 h at the metabolic ward and given either 6 isoenergetic meals, i.e., every 4 h (N-eat) or 4 isoenergetic meals from 0800 to 2000 h followed by a nocturnal fast (N-fast), with the same 24-h energy intake. Energy expenditure, substrate utilization, activity, heat release, body temperature and blood variables were measured over 24 h. Energy expenditure and blood glucose, triacylglycerol, insulin and glucagon concentrations were lower and nonesterified fatty acids concentrations were higher during the nocturnal fast than during nocturnal eating (P < 0.05); however, no 24-h differences between the protocols were apparent. Nocturnal fasting slightly altered the secretory patterns of the thyroid hormones and cortisol (P < 0.05). We found no clear indication that it would be more favorable to ingest few larger daytime meals than smaller meals throughout the 24-h period. The body seems to be able to buffer small differences in meal size and timing provided energy balance is maintained.     

Patterns of plasma leptin and insulin concentrations in hospitalized patients after the initiation of total parenteral nutrition

BACKGROUND: The regulation of leptin in patients with critical illness is poorly understood. Sex, diet, body mass, and cytokines may all play a role. OBJECTIVE: The aims of this study were to determine the factors influencing leptin concentrations in hospitalized patients beginning total parenteral nutrition (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin concentrations above baseline. DESIGN: Twenty-six patients requiring TPN were enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men) completed all 3 d of TPN. RESULTS: Baseline plasma leptin in the TPN patients ranged from 62.5 to 1625 pmol/L ( +/- SD: 419 +/- 387; n = 26) and was not significantly different between men (444 +/- 494 pmol/L) and women (363 +/- 244 pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 +/- 188; n = 26) and was not correlated with plasma leptin. Leptin concentrations increased after 3 d of TPN, from 356 +/- 300 to 794 +/- 600 pmol/L (P < 0.05) in parallel with an increase in insulin from 257 +/- 187 to 979 +/- 917 pmol/L (P < 0.01) in the 20 patients who completed the study; however, the changes were not correlated when expressed as percentages. Although the men and women had insulin responses to feeding that were not significantly different, leptin concentrations did not increase significantly in men but increased 3-fold in women (to 1094 +/- 638 pmol/L; P < 0.01). CONCLUSIONS: Leptin regulation in patients with a critical illness differs substantially from that in healthy persons. The importance of glucose and insulin in leptin secretion remains unclear, especially in men.     

Overnourishing pregnant adolescent ewes preserves perirenal fat deposition in their growth-restricted fetuses

Overnourishing the adolescent sheep promotes rapid maternal growth at the expense of the gravid uterus. The growth of the placenta is impaired and results in the premature delivery of low-birthweight lambs. The present study details fetal adipose tissue development in these growth-restricted pregnancies. Singleton pregnancies were established by embryo transfer and, thereafter, adolescent ewes were offered a high (H; n = 12) or moderate (M; n = 14) level of a complete diet until necropsy on Day 131 of gestation. Fetal weight was lower (P < 0.001) in H compared with M groups. High maternal intake preserved brain and perirenal fat weight (P < 0.003), whereas relative weights of the heart, lungs, spleen and liver were unaltered. High nutrient intake resulted in significantly elevated maternal plasma concentrations of insulin, leptin, prolactin and glucose, no significant changes in fetal insulin, leptin or non-esterified fatty acids and attenuated fetal prolactin concentrations. Irrespective of nutritional intake, maternal plasma leptin, prolactin and glucose concentrations were negatively correlated with fetal weight and were positively correlated with fetal perirenal fat proportion (all P < 0.01). The mRNA expression for leptin, prolactin receptor and uncoupling protein (UCP) 1 in fetal perirenal fat was equivalent between groups, but, irrespective of maternal nutrition, UCP1 mRNA levels were negatively correlated with fetal weight (P < 0.01). Thus, overnourishing pregnant adolescent sheep preserves fat deposition in their growth-restricted fetuses, which may have implications for neonatal thermogenesis and for programming of postnatal adiposity.     

High leptin in pregnant mink (Mustela vison) may exert anorexigenic effects: a permissive factor for rapid increase in food intake during lactation

The role for leptin in food intake regulation in the mink, a polytocous seasonal breeder with altricial young, was investigated in pregnant and lactating dams and data were related to quantitative energy metabolism measurements and plasma concentrations of other important metabolic hormones. A total of nine mink dams were measured in consecutive 1-week balance periods, each including a 22 h measurement of heat production by means of indirect calorimetry, and blood was sampled at weekly intervals throughout gestation and during lactation weeks 1-4. Intake of metabolisable energy (ME) was high and energy balance was positive until the first third of true gestation. During mid- and late gestation ME intake decreased (P<0.001) while heat production remained almost constant, resulting in negative energy balance and the loss of body weight. From late gestation until lactation week 4, ME intake increased by 3.5 times, but weight loss continued. Plasma concentrations of leptin were approximately doubled during the last two-thirds of true gestation (P<0.01), demonstrating a clear gestational hyperleptinaemia. Concentrations declined rapidly after parturition and then remained stable. Insulin was independent of leptin, with low concentrations coincident with hyperleptinaemia. Also, concentrations of thyroid hormones declined during gestation, probably reflecting the low food intake. Hyperleptinaemia concomitant with low ME intake, negative energy balance and mobilisation of body reserves suggested an anorexigenic effect of leptin in pregnant mink. This suppression of food intake in late gestation might be permissive for the rapid increase in food intake occurring after parturition.     

Blunted lipolytic response to fasting in abdominally obese women: evidence for involvement of hyposomatotropism

BACKGROUND: Abdominal obesity is associated with a blunted lipolytic response to fasting that may contribute to the preservation of adipose tissue mass. OBJECTIVE: To further explore the pathophysiology of blunted lipolysis during fasting in obesity, we simultaneously measured lipolysis and distinct neuroendocrine regulatory hormones in abdominally obese and normal-weight (NW) women. DESIGN: Eight abdominally obese [x +/- SD body mass index (BMI; in kg/m(2)): 32.1 +/- 2.6] and 6 NW (BMI: 22.7 +/- 1.5) women were studied during the last 8 h of a 20-h fast. The glycerol appearance rate and the serum and plasma concentrations of insulin, leptin, cortisol, and growth hormone were measured regularly. RESULTS: At 13 h of fasting, the mean (+/-SD) glycerol appearance rate corrected for fat mass was greater in NW women than in obese women (7.2 +/- 1.0 and 5.1 +/- 0.6 micro mol.kg(-1).min(-1), respectively; P = 0.001). After a 20-h fast, lipolysis increased to 8.9 +/- 1.5 mmol.kg(-1).min(-1) in NW women (23%), whereas it did not change significantly in obese women (-2%). Fasting decreased insulin concentrations by approximately 30% in both groups, but it did not induce significant changes in leptin concentrations. Mean cortisol concentrations and urinary catecholamine excretion were comparable in both groups. However, mean plasma growth hormone concentrations were higher in NW women than in obese women (1.81 +/- 0.98 compared with 0.74 +/- 0.52 mU/L; P = 0.046). The relative change in lipolysis tended to correlate with mean plasma growth hormone concentrations (r = 0.515, P = 0.059). CONCLUSION: Abdominal obesity-associated hyposomatotropism may be involved in the blunted increase in lipolysis during fasting.     

Metabolic advantages of spreading the nutrient load: effects of increased meal frequency in non-insulin-dependent diabetes.

The acute effect of increasing meal frequency as a model of slow absorption was studied for 1 d in 11 patients with non-insulin-dependent diabetes. On 1 d they took 13 snacks (the nibbling diet) and on another day the same diet was taken as three meals and one snack (the three-meal diet). The nibbling diet reduced mean blood glucose, serum insulin, and C peptide concentrations over the 9.5 h of observation and 24-h urinary C peptide output by 12.7 +/- 3.7% (mean +/- SE) (P = 0.0062), 20.1 +/- 5.8% (P = 0.0108), 9.2 +/- 2.6% (P = 0.0073), and 20.37 +/- 8.12% (P = 0.039), respectively, compared with the three-meal diet. Serum triglyceride concentrations were lower by 8.5 +/- 3.2% (P = 0.037). Despite lower insulin concentrations on the nibbling diet, the concentrations of free fatty acids, 3-hydroxybutyrate, and the insulin-sensitive branched-chain amino acids responded similarly on both treatments. Metabolic benefits seen with increased meal frequency may explain the success of similar agents that prolong absorption, including fiber and enzyme inhibitors.     

Role of male novelty and familiarity in male-induced LH secretion in female sheep

Ewes supposedly need to be separated from rams before male stimuli can increase gonadotrophin secretion and induce ovulation. In the present study, we investigated the LH response of ewes to 'novel' and 'familiar' rams after varying periods of separation. In Experiment 1, ewes (n = 8 per treatment) were separated from familiar rams for 15 min or 1 month and then exposed to either familiar rams, novel rams or novel wethers. After 15 min or 1 month of separation, exposure to novel rams increased pulsatile LH secretion (P < 0.05) and induced an LH surge in all ewes whereas exposure to familiar rams or novel wethers had no effect on LH secretion (P > 0.1). After 1 month of separation, re-exposure to the same familiar rams increased pulsatile LH secretion (P < 0.05) in six of eight ewes, but only induced an LH surge in two of eight ewes. In Experiment 2, familiar rams were removed and returned after 15 min, 1 day or 17 days (n = 5 per treatment). None of these treatments affected LH secretion. We conclude that separation of ewes from rams is a prerequisite for familiar rams to increase LH secretion, but is not necessary if the rams are novel.     

Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.