Regulation of insulin sensitivity by adiponectin and its receptors in response to physical exercise.

Adiponectin is an adipocyte-derived abundant plasma protein, also called Acrp30 (adipocyte complement-related protein), adipoQ, ApM1 (AdiPose Most abundant Gene transcript 1), or GBP28 (gelatin-binding protein-28). Insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-α pathways, respectively. In the same sense chronic exercise has been showed to induce numerous metabolic factors that can improve insulin resistance. It has been reported that physical exercise training increases adiponectin receptors, which may mediate the improvement of insulin resistance in response to exercise, which is the focus of the present review.

Resveratrol prevents hyperleptinemia and central leptin resistance in adult rats programmed by early weaning.

We have previously shown that early weaning in rats increases the risk of obesity and insulin resistance at adulthood, and leptin resistance can be a prime factor leading to these changes. Resveratrol is reported to decrease oxidative stress, insulin resistance, and cardiovascular risk. However, there is no report about its effect on leptin resistance. Thus, in this study we have evaluated resveratrol-preventing effect on the development of visceral obesity, insulin, and leptin resistance in rats programmed by early weaning. To induce early weaning, lactating dams were separated into 2 groups: early weaning (EW)--dams were wrapped with a bandage to interrupt lactation in the last 3 days of lactation and control (C)--dams whose pups had free access to milk during throughout lactation period (21 days). At 150 days-old, EW offspring were subdivided into 2 groups: EW+res--treated with resveratrol solution (30 mg/kg BW/day) or EW--receiving equal volume of vehicle solution, both given by gavage during 30 days. Control group received vehicle solution. Resveratrol prevented the higher body weight, hyperphagia, visceral obesity, hyperleptinemia, hyperglycemia, insulin resistance, and hypoadiponectinemia at adulthood in animals that were early weaned. Leptin resistance, associated with lower JAK2 and pSTAT3 and higher NPY in hypothalamus of EW rats were also normalized by resveratrol. The present results suggest that resveratrol is useful as therapeutic tool in treating obesity, mainly because it prevents the development of central leptin resistance.

Time of physical exercise practice after injury in cervical spinal cord-injured men is related to the increase in insulin sensitivity.

OBJECTIVES: Physical exercise has an important role in reducing body fat, risk of chronic disease and systemic inflammation. The aim of this study was to determine serum leptin and insulin concentrations and their relationship to the time of physical exercise after injury in men with cervical spinal cord injury (c-SCI). METHODS: c-SCI subjects with lesion level in C5-C7 (n=25) were divided into two groups: physically active (PA, n=13; those who practiced physical exercise for at least 3 months, three times per week or more, for a total minimum of 150 min of physical activity per week) and non-physically active (N-PA, n=9). Body composition was assessed by dual energy X-ray absorptiometry. Blood samples were obtained 12 h after an overnight fast to measure insulin and leptin in serum, and glucose and C-reactive protein (CRP) in plasma, by validated methods. RESULTS: Comparing the PA and N-PA group, the first presented lower: total body mass (-13%), body mass index (-16%), fat mass (kg -39%, FM% -30%), CRP (-23%), serum insulin (-61%), homeostasis model assessment (HOMA, -35%) and serum leptin (-62%; P<0.05). Both serum insulin (r=-0.561; P<0.05) and HOMA (r=-0.591; P<005) were inversely proportional to the time of practice of physical activity after injury. CONCLUSION: Our results suggest that exercise was able to reduce fat mass and increase insulin sensitivity, decreasing plasma levels of risk factors in c-SCI subjects.

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats.

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 µg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.

Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-ß estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups.

Postnatal low protein diet programs leptin signaling in the hypothalamic-pituitary-thyroid axis and pituitary TSH response to leptin in adult male rats.

Maternal protein restriction (PR) during lactation programs a lower body weight, hyperthyroidism, leptin resistance, and over-expression of leptin receptor in the pituitary gland at adulthood. Because leptin regulates energy homeo-stasis and the hypothalamus-pituitary-thyroid (HPT) axis, we evaluated adipocyte morphology, the leptin signaling pathway in the HPT axis and the in vitro thyrotropin (TSH) response to leptin in adult progeny in this model. At birth, dams were separated in control diet with 23% protein or PR diet with 8% protein. After weaning, offspring received a normal diet. Adult PR offspring showed lower adipocytes area, higher leptin:visceral fat ratio, lower hypothalamic signal transducer and activator of transcription 3 (STAT3), higher pituitary leptin receptor (Ob-R) and lower thyroid janus tyrosine kinase 2 (JAK2) contents. Regarding the in vitro study, 10(-7) M leptin stimulated TSH secretion in C offspring at 30 min, but had no effect in PR offspring. At 120 min, 10(-7) M leptin decreased TSH secretion in C offspring and increased in PR offspring. Maternal nutritional status during lactation programs for adipocyte atrophy, higher relative leptin secretion and changes in the downstream leptin signaling in the HPT axis and the TSH response to leptin, suggesting a role for leptin in the development of the HPT axis and helping to explain thyroid dysfunction and leptin resistance in this programming model. Because leptin stimulates thyroid function, it is unlikely that these alterations were responsible for the increased in serum T4 and T3. Therefore, neonatal PR programs a hyperthyroidism, lower adipogenesis, and impairment of leptin action.

Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.

Maternal prolactin inhibition during lactation is associated to renal dysfunction in their adult rat offspring.

The renal function of rats whose mothers had hypoprolactinemia at the end of lactation was evaluated during development. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg twice a day, s.c.) or saline on days 19, 20, and 21 of lactation, and their male offspring were followed from weaning until 180 days old. 1 rat from each of the 12 litters/group was evaluated at 2 time points (90 and 180 days). Body and kidney weights, sodium, potassium, and creatinine were measured. Values were considered significant when p<0.05. Adult BRO-treated offspring presented higher body weight (+10%), lower relative renal weight at 90 and 180 days (-9.2% and -15.7%, respectively), glomerulosclerosis, and peritubular fibrosis. At 90 and 180 days, creatinine clearance was lower (-32% and -30%, respectively), whereas serum potassium was higher (+19% and +29%, respectively), but there were no changes in serum sodium. At 180 days, higher proteinuria (+36%) and serum creatinine levels (+20%) were detected. Our data suggest that prolactin inhibition during late lactation programs renal function damage in adult offspring that develops gradually, first affecting the creatinine clearance and potassium serum levels with further development of hyperproteinuria and higher serum creatinine, without affecting sodium. Thus, precocious weaning programs some components of the metabolic syndrome, which can be a risk factor for further development of kidney disease.

Blocking leptin action one week after weaning reverts most of the programming caused by neonatal hyperleptinemia in the adult rat.

Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected or leptin-injected from postnatal day 1 to day 10. At 29 and 30 days old, animals were injected with anti-leptin antibody (LA and CA) or saline (LS and CS). In adult animals, higher visceral (+53%) and total fat mass (+33%), hyperleptinemia (+67%), hypertriglyceridemia (+47%), and hypoadiponectinemia (-44%) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin-treated animals, in addition to lower serum adiponectin (-77% vs. CS) and higher insulin resistance index (+37%). Liver sirtuin1 (SIRT1) was higher (+41%) only in LA group, suggesting a role for SIRT1 in the prevention of leptin programming. Hypothalamic OBR was lower and SOCS3 higher in LS group and these changes were normalized in LA group. In conclusion, blocking leptin action one week after weaning seems to revert most of the alterations observed in rats programmed by neonatal hyperleptinemia. Higher liver SIRT1 expression may be one of the mechanisms involved, leading to a better glucose and lipid metabolism. Our data suggest that the lack or the excess of leptin programs an adverse metabolic phenotype in adulthood.

Neonatal nicotine exposure alters leptin signaling in the hypothalamus-pituitary-thyroid axis in the late postnatal period and adulthood in rats.

AIMS: Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring. MAIN METHODS: Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05. KEY FINDINGS: In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%). SIGNIFICANCE: Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.

Prolactin inhibition at mid-lactation influences adiposity and thyroid function in adult rats.

Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition model) on milk leptin transfer, leptinemia, body composition, and thyroid function. Lactating rats were treated with bromocryptine (BRO, 1 mg/twice daily) or saline on days 7, 8, and 9 of lactation. Offspring were sacrificed 10, 21, and 90 days after birth. After treatment, BRO-treated dams showed hypoprolactinemia and hyperleptinemia, and produced less milk with lower levels of lactose and higher milk triglycerides. Milk leptin levels were lower at weaning. Offspring of BRO-treated dams had lower body weight and length as well as less visceral fat during lactation and adulthood. Total fat was also lower at weaning and adult life, whereas total protein was higher at 90 days-old. BRO offspring presented lower serum T4 and TSH at 10 days-old and weaning, respectively. When adults, these rats exhibited hypoleptinemia, lower levels of thyroid hormones, and higher TSH. Early inhibition of PRL therefore leads to offspring malnutrition and affects subsequent growth. Also, inhibition of PRL during lactation predisposes offspring to hypothyroidism; however, when the inhibition occurs during late lactation, the hypothyroidism is secondary, whereas when it is restricted to mid-lactation, the thyroid hypofunction is primary. The programming effect of milk suppression thus depends on the developmental stage of offspring.

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway.

Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (+78% and 2-fold increase, respectively; P < 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P < 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (-17%, P < 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (-22%, P < 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (-61% and -29%, respectively, P < 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (+2-fold, P < 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension.

Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats.

We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC - continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C - saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were P<0.05. At the end of nicotine exposure (15 days), dams presented higher milk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.

Leptin treatment during lactation programs leptin synthesis, intermediate metabolism, and liver microsteatosis in adult rats.

Epidemiological and experimental studies have associated development of metabolic syndrome with stressful events (nutritional, hormonal, or environmental) in early life. This phenomenon is known as programing and changes in adipokines levels in early life, especially leptin, seem to be involved with its development. We have shown that neonatal hyperleptinemia on lactation programs for leptin resistance, hyperthyroidism, and higher corticosterone and catecholamines levels with cardiovascular consequences. In the present study, we evaluated the effect of hyperleptinemia during lactation on the glucose and lipid metabolism and liver morphology of adult rats, which were saline or leptin-treated (8 microg/100 g of body weight) daily, for the first 10 days of life. Leptin group had lower body mass during treatment, but higher body mass and hyperleptinemia at adulthood, without difference in fat mass. We showed that the probable source of hyperleptinemia is the higher leptin content in the subcutaneous adipose tissue. The programed rats showed hyperinsulinemia and hypoadiponectinemia with higher expression of the hypothalamic Suppressor of Cytokine Signaling 3 (SOCS3), suggesting insulin resistance. Besides, they presented higher liver glycogen and hypertriglyceridemia. We also observed liver microsteatosis in the leptin-programed adult rats. Our data show that neonatal hyperleptinemia alters glucose metabolism, which seems to be partially compensated by the hyperinsulinemia. However, changes in the lipid metabolism are not compensated. It is probable that these changes induced by neonatal hyperleptinemia result from a selective tissue specific resistance both to insulin and leptin at adulthood, and the increase of SOCS3 may play an important role in this process.

Maternal flaxseed diet during lactation alters milk composition and programs the offspring body composition, lipid profile and sexual function.

We evaluated the effects of maternal dietary flaxseed during lactation on milk composition, body composition and sexual function of the adult female offspring. The dams were fed a control casein diet (C) or flaxseed diet (F, 25%) throughout lactation. F mothers showed higher serum 17beta-estradiol (E2) and leptin at weaning. F mother's milk had lower total cholesterol (TC) and higher E2 and leptin. The offspring of F dams showed lower body mass (BM), body fat mass (BFM), visceral fat mass (VFM), TC and triglycerides (TG) and higher serum leptin and E2 at 21 days. F offspring showed delayed puberty onset. At 150 days, these offspring presented higher BFM, VFM, TC, TG, E2 and lower relative uterine weight and lower progesterone. In conclusion, flaxseed during lactation did affect the lipid profile, adipose tissue and sexual function in adulthood, probably due hyperestrogenism and hyperleptinemia at weaning.

Early maternal hyperleptinemia programs adipogenic phenotype in rats.

We have previously reported on the treatment of maternal rats with leptin during the three last days of lactation program for overweight and leptin hypothalamic resistance in the offspring. Here we have investigated whether treatment of maternal rats with leptin in the first ten days of lactation can program metabolic dysfunctions on the adult offspring. Lactating rats were divided into 2 groups: rats (LEP) injected with recombinant mouse leptin (8 microg/100 g/body weight, daily during the first 10 days of lactation) and control group (C) that received the same volume of saline. After weaning, all pups had free access to normal diet, their body weight and food intake were monitored at 4 days interval until 180 days, when they were tested for food intake and response to either leptin (0.5 mg/kg body weight, ip) or saline. The offspring from leptin-treated mothers gained more weight from day 69 onward and had higher food intake from day 145 onward, higher amount of visceral adipose tissue (57%), higher serum glucose (10%), and higher serum leptin (135%) at 180 days compared to control group. The food intake was not reduced as expected after acute injection of leptin in these animals, suggesting resistance to the anorexigenic effect of leptin. We conclude that maternal hyperleptinemia in early lactation programed higher food intake, body weight gain due to higher total and visceral fat mass, and resistance to anorexigenic effect of leptin in the adult offspring even when this hyperleptinemia occurred at the beginning of lactation.

Temporal evaluation of body composition, glucose homeostasis and lipid profile of male rats programmed by maternal protein restriction during lactation.

Neonatal protein restriction causes lower body weight and hormonal dysfunctions in 6 months-old rats. In this model, we studied the body composition, glycogen content, serum lipid, serum protein, and hormones related to glucose homeostasis in the offspring during development. At birth, lactating rats were divided into: control dams - fed a normal diet (23% protein) and protein restricted dams - fed a diet with 8% protein. After weaning, pups received normal diet. Offspring were killed at 21, 90, and 180 days-old. Protein restricted offspring showed lower visceral fat (90th day: 14%; 180th day: 19%) and lower total fat (90th day: 16%; 180th day: 14%) that explain their lower body weight. They presented lower glycemia (180th day: 17%), lower insulinemia (21st day: 63%; 180th day: 24%), higher adiponectinemia (21st day: 169%), higher liver glycogen (21st day: 104%), and higher muscle glycogen (180th day: 106%), suggesting a higher insulin sensitivity. The higher serum corticosterone (50%), higher adrenal total catecholamines content (98%) as well as in vitro catecholamine secretion (26%) of adult protein restricted offspring, suggest a programming stimulatory effect upon adrenal gland. They also presented several biochemical changes, such as lower serum total protein, albumin and globulin (21st day: 17, 21, 12%, respectively), higher LDL-c (21st day: 69%), lower triglycerides (21st day: 42%; 90th day: 39%), and lower total cholesterol (180th day: 16%). Thus, maternal protein restriction during lactation induces an energy-protein malnutrition, characterized by an impairment of the pup's protein anabolism and, after weaning, the lower adiposity suggests lower lipogenesis and higher lipolytic activity, probably caused by catecholamine and glucocorticoid action.

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring.

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor.

Ultrasound and CT findings in hepatic and pancreatic parenchyma in acute schistosomiasis.

A case of acute toxaemic schistosomiasis is presented. Abdominal ultrasound examination revealed hepatosplenomegaly, lymphadenomegaly, heterogeneous hepatic parenchyma and heterogeneous focal lesions in the pancreas. CT confirmed lymph node enlargement and hepatosplenomegaly, and showed multiple small focal nodular lesions in the liver and focal lesions in the pancreas. To our knowledge, this is the first description of pancreatic lesions associated with acute Schistosoma mansoni infection.

Neonatal programming of neuroimmunomodulation--role of adipocytokines and neuropeptides.

Programming is an epigenetic phenomenon by which nutrition, environment and stress acting in a critical period earlier in life change the organism's development. This process was evolutionarily selected as an adaptive tool for the survival of organisms living in nutritionally deficient areas and submitted to stressful conditions. Thus, perinatal malnutrition turns on different genes that provide the organism with a thrifty phenotype. In conditions of abundant supply of nutrients, those programmed organisms can be at risk of developing metabolic diseases (obesity, dyslipidemia, diabetes and hypertension). How nutrition or neonatal stress can program the immune system is less well known. Here, we discuss some of the hormonal and metabolic changes that occur in mothers and neonates and how those factors can imprint hormonal or metabolic changes that program neuroimmunomodulatory effects. Some of these changes involve thyroid hormones, leptin, insulin, glucocorticoids and prolactin as potential imprinting factors. Most of them can be transferred through the milk and may change with malnutrition or stress. We discuss the programming effects of these hormones upon body weight, body composition, insulin action, thyroid, adrenal and immune and inflammatory responses, with special emphasis on leptin, a cytokine that seems to play a central role in these events.