[Show abstract][Hide abstract] ABSTRACT: The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82 % in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model.
[Show abstract][Hide abstract] ABSTRACT: Gut peptides regulate appetite and adipogenesis. Early weaning (EW) leads to later development of obesity, which can be prevented by calcium supplementation. We evaluated gut peptides that may have a role in the establishment of this dysfunction.
At birth, lactating Wistar rats were separated in: EW, lactating rats involved with a bandage interrupting the lactation during the last 4 days of standard lactation, and C (control), dams whose pups had free access to milk during throughout lactation. At 120 days-old, half of EW group received calcium supplementation (EWCa); EW and C received standard diet. At 21 days-old, EW presented higher GLP-1 in plasma and GLP1-R in adipose tissue and hypothalamus, but lower GLP-1 and GLP1-R in the gut. At 180 days-old, GLP-1 response to food intake was blunted in EW and restored by calcium. GLP-1 in the gut was lower in EW and its receptor was lower in adipose tissue, and GLP1-R was higher in the gut of EWCa.
Thus, EW had short and long-term effects upon GLP-1 profile, which may have contributed to obesity development, hyperphagia and insulin resistance, due to its adipogenic and appetite control roles. Calcium supplementation was able to prevent most of the changes in GLP-1 caused by EW. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Molecular Nutrition & Food Research 01/2015; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and how it develops during the nutritional transition from milk through solid food. Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5 mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food intake, body mass, and body length. At PN30, only body length and mesenteric fat mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue leptin mRNA expression was lower, while plasma leptin was higher in PN30, possibly due to a higher adipose mesenteric tissue production. At PN22, the hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST, suggesting a liver dysfunction. Our data show that milk supply can exert a crucial role in the imprinting of a second leptin peak, which is important for survival adaptation to adverse nutritional conditions.
Hormone and Metabolic Research 11/2014; · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: we evaluated the effects of yerba mate treatment over 30days on body weight, food intake, hypothalamic leptin action and inflammatory profile in adult rats that were weaned early.
[Show abstract][Hide abstract] ABSTRACT: We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil + 2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2014; · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Childhood obesity is growing in prevalence. Obesity and bone dysfunctions may be related disorders, and therefore our aim was to study the impact of the early overfeeding (EO) in offspring bone health since weaning up to adulthood. To induce EO during lactation, litter size was adjusted to 3 male rats per litter (SL). Litter containing 10 pups per mother was the control (NL). Bone tissue was evaluated by dual-energy X-ray absorptiometry, computed tomography, microcomputed tomography, biomechanical tests, and serum analyses. SL offspring presented higher body weight, fat mass, lean mass from 21 up to 180 days, hyperphagia, and higher visceral fat mass. Bone analysis showed that SL offspring presented higher total bone mineral density (BMD) only at 180 days, and higher total bone mineral content and higher bone area from 21 until 180 days. At 180 days, SL offspring presented higher femur BMD and fourth lumbar vertebra (LV4) BMD, higher femoral head radiodensity and LV4 vertebral body radiodensity, lower trabecular pattern factor and trabecular separation, however with higher trabecular number, higher maximal load, resilience, stiffness and break load, and lower break deformation. SL group had, at 180 days, higher osteocalcin and lower C-terminal cross-linked telopeptide of type I collagen (CTX I). We have shown that the excess of fat mass contributed to an increased bone mass, and hypothesized that this increase could be mediated by the hypothyroidism and previous higher thyroid hormone action and hyperleptinemia at weaning. Furthermore, the increased biomechanical loading due to increased body weight probably help us to understand the protective effects obesity exerts upon bone health.
Hormone and Metabolic Research 03/2014; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies have demonstrated that early weaning can promote metabolic syndrome during adulthood and that obesity increases oxidative stress. Thus, we aimed to evaluate redox status in a pharmacological early weaning rodent model programmed for metabolic syndrome at adulthood.
Lactating dams were randomly assigned into 2 groups: the early weaning group (BRO), which was treated intraperitoneally with bromocriptine (1mg/day) to inhibit prolactin secretion for the last 3days of lactation, and the control group (C), which received the BRO diluent for the same time period. The offspring were killed at 90 (PN90) and 180 (PN180) days after birth.
Early weaning induced greater visceral adiposity and dyslipidemia. At PN90, the BRO offspring showed glucose intolerance with normoinsulinemia and increased plasma and liver superoxide dismutase, and liver glutathione peroxidase activities, which reduced the liver malondialdehyde but not the increased plasma malondialdehyde levels. However, the BRO offspring showed insulin resistance at PN180 and increased plasma glutathione peroxidase, liver superoxide dismutase, and catalase activities. These changes reduced the plasma and liver malondialdehyde levels, which aided in hepatocyte architecture preservation. Additionally, we observed that sirtuin 1 was overexpressed in the BRO group at PN90, but the increased expression was not maintained through PN180, which suggests unfavorable metabolic conditions in the older offspring. Significance Despite the observed obesity and glucose homeostasis dysfunction, our data suggest that the early weaning programming induced by bromocriptine can improve the offspring's redox status and may prevent liver damage during adulthood.
[Show abstract][Hide abstract] ABSTRACT: The most frequently used animal models of early weaning (EW) in rodents, maternal deprivation and pharmacological inhibition of lactation, present confounding factors, such as high stress or drug side effects, that can mask or interact with the effects of milk deprivation per se. Given these limitations, the development of new models of EW may provide useful information regarding the impact of a shortened period of breastfeeding on the endocrine and nervous systems, both during development and at adulthood. Using a model of EW in which lactating Wistar rat dams are wrapped with a bandage to block access to milk during the last three days of lactation, we have recently shown that the adult offspring presented higher body mass, hyperphagia, hyperleptinemia, leptin as well as insulin resistance, and higher adrenal catecholamine contend at adulthood. Here, we used this EW model, which involves no pharmacological treatment or maternal separation, to analyze anxiety-like, novelty-seeking and memory/learning behavioral traits in the adult male offspring. To that end, animals were tested in the elevated plus maze, in the hole board arena and in the radial arm water maze. Except for an increased number of rearing events (a measure of vertical activity), no other behavioral differences were observed between EW and control animals. The contrasting behavioral results between the three EW models may be associated with differences in HPA axis function in the offspring at weaning, since it has been observed that bandaging does not affect corticosteronemia while maternal separation and pharmacological EW increases it.
[Show abstract][Hide abstract] ABSTRACT: The inhibition of maternal prolactin production in late-lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20 and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into: sedentary and trained controls (C-Sed, C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed, Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome, and were reversed in Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, the liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma LDH (lactate dehydrogenase) levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats.
Journal of Endocrinology 07/2013; · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signalling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2(nd) postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6mg/Kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had P<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fibre density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013; · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children from pregnant smokers show more susceptibility to develop obesity in adult life. Previously, we failed to demonstrate in rats offspring a programming for obesity when only the mothers were tobacco smoke-exposed during lactation. Here, we studied the short- and long-term effects of smoke exposure to both dams and their pups during lactation upon endocrine and metabolic parameters. For this, we designed an experimental model where nursing rats and their pups were divided into: SE group, smoke-exposed in a cigarette smoking machine (4 times/day, from the 3rd to the 21th day of lactation) and C group, exposed to filtered air. Pups were killed at 21 and 180 days old. At weaning, SE pups showed lower body weight (7%), length (5%), retroperitoneal fat mass (59%), visceral adipocyte area (60%) and higher subcutaneous adipocyte area (95%) with hypoinsulinemia (-29%), hyperthyroxinemia (59%), hypercorticosteronemia (60%) and higher adrenal catecholamine content (+58%). In adulthood, SE offspring showed higher food intake (+10%), body total fat mass (+50%), visceral fat mass (retroperitoneal: 55%; mesenteric: 67%; epididymal: 55%), and lower subcutaneous adipocyte area (24%) with higher serum glucose (11%), leptin (85%), adiponectin (1.4 fold-increase), TT3 (71%), FT4 (57%), TSH (36%), triglycerides (65%), VLDL-c (+66%), HDL-c (91%) levels, lower corticosteronemia (41%) and adrenal cathecolamine content (57%). Our present findings suggest that tobacco smoke exposure to both dams and their pups during lactation causes a malnutrition in early life that programs for obesity and hormonal and metabolic disturbances in adulthood, only if the pups are submitted to the same smoke environment than the mother.
Journal of Endocrinology 04/2013; · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effects of maternal malnutrition during lactation on the kidneys in mice infected with Schistosoma mansoni. Kidneys from programmed infected mice and their respective controls fed a normal diet (23% protein), a protein-restricted group (PR) (8% protein) and a caloric-restricted group (CR) (according to the PR group intake) evaluated by biometry, morphometry and histopathology. Both PR and CR groups showed a reduction in the number of glomeruli when compared with the control group (CR:-29% vs C; PR:-41% vs C; p < 0.05) as well as infected mice (ICR:-32% vs IC; IPR:-47% vs IC; p < 0.05). Among infected mice, ICR group showed higher kidney weights (+18% vs IC and +12% vs IPR; p < 0.01). The ICR and IPR groups showed largest perimeter and area when compared to the corresponding uninfected group (ICR vs CR:+26%; IPR vs PR:+21%, p < 0.05) and area (ICR vs CR:+95%; IPR vs PR:+50%, p < 0.05). The ICR group showed an increase of within Bowman (CR vs ICR + 56%, p < 0.05), whereas Bowman's space was reduced (PR vs IPR, -61%; p < 0.05). Conclude that malnutrition during lactation programmed the metabolic state of the host, resulting in the evolution of the histology of the renal parenchyma.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content. METHODS: To induce early weaning, lactating rats' teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed. RESULTS: EW+ mate group presented lower body weight (-10 %), adipose mass (retroperitoneal:-40 % and epididymal:-44 %), total body fat (-43 %), subcutaneous fat (-46 %), visceral adipocyte area (-21 %), triglyceridemia (-31 %) and hypothalamic NPY content (-37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored. CONCLUSION: Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model.
European Journal of Nutrition 02/2013; · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Obesity and osteoporosis seems to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism.
Lactating rats were separated into 3 groups: control - dams whose pups ate milk throughout lactation; mechanical EW (MEW) - dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW) - dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) 3 days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses.
MEW and PEW presented total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups.
Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass.
Metabolism: clinical and experimental 01/2013; · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During the last decade a great concern has developed for determining what factors influence bone mineral accretion in healthy children. Mother's milk represents the primary source of calcium and other nutrients in the neonate. The development of bone and adipose tissue has common origins. Since early weaning decreases adipogenesis in neonate, our aim was to evaluate bone metabolism in 2 models of early weaning (EW) in neonate rats. Lactating rats were separated into 3 groups: control: pups had free access to milk; MEW: dams were involved with a bandage mechanically (M) interrupting lactation in the last 3 days; and PEW: dams were pharmacologically (P) treated to block prolactin (0.5 mg bromocryptine/twice a day) 3 days before standard weaning. Significant difference had p<0.05. At weaning, MEW and PEW pups presented lower body weight ( - 18% and - 15%), total body fat ( - 26% and - 27%), total bone mineral density ( - 7% and - 6%), total bone mineral content ( - 30% and - 32%), bone area ( - 28% and - 30%), serum osteocalcin ( - 20% and - 55%), and higher C-terminal cross-linked telopeptide of type I collagen (CTX-I) (1.3 and 1.1-fold increase). However, serum ionized calcium was lower only in MEW pups ( - 34%), 25-hydroxyvitamin D was higher (1.4-fold increase), and PTH was lower ( - 26%) only in PEW group. The present study shows that both early weaning models leads to an impairment of osteogenesis associated with lower adipogenesis by different mechanisms, involving mainly changes in vitamin D and PTH.
Hormone and Metabolic Research 12/2012; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that resveratrol, a natural phytoalexin found in grapes, can prevent oxidative stress, obesity and its related disturbances in obese rats programmed by early weaning. Lactating Wistar rats were separated into two groups: early weaning (EW) - dams who were wrapped with a bandage to interrupt the lactation in the last 3 days of lactation; control - dams whose pups had free access to milk during all lactation. At the 150th day, EW offspring were randomly subdivided into EW+resveratrol (EW+Res) - resveratrol (30 mg/kg/day); EW+vehicle (EW) - rats that received 0.5% (w/v) aqueous methylcellulose. The control group received vehicle. Rats were treated by gavage daily for 30 days. EW offspring developed hyperphagia, higher body weight, visceral obesity, higher systolic (SBP) and diastolic blood pressure (DBP) (+15% and +20%, respectively; P<.05) and higher serum triglycerides (TG) and low-density lipoprotein but lower high-density lipoprotein (+55%, +33% and -13%, respectively; P<.05). Resveratrol normalized food intake, SBP and DBP and prevented obesity and dyslipidemia in EW+Res. EW rats had higher plasma and liver thiobarbituric-acid-reactive substances (TBARS) and lower plasma superoxide dismutase (SOD) and liver glutathione peroxidase activities (+51%, +18%, -58%, -31%, respectively; P<.05), and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma. EW rats presented liver steatosis and higher liver TG, and resveratrol prevented these hepatic alterations. In conclusion, this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension, dyslipidemia and steatosis in adult rats programmed by early weaning.
The Journal of nutritional biochemistry 09/2012; · 4.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning) - dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control - dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area ( - 67.7% and - 62%, respectively), body fat mass ( - 26%), and leptin expression in visceral adipocyte ( - 64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 ( - 55%) and TSH ( - 44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRβ3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue ( - 40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.
Hormone and Metabolic Research 09/2012; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postnatal early overfeeding (EO) is related to later development of overweight and other metabolic disorders. As oxidative stress is implicated in most human diseases, as obesity and diabetes, we decided to study some parameters related to oxidative stress and insulin signaling in liver from EO animals in adult life. To induce EO, litter size was reduced to three pups per litter (SL: small litter) and groups with normal litter size (NL:10 pups per litter) were used as control. After weaning, rats had free access to standard diet and water. Body weight and food intake were monitored daily and offspring were killed at 180 days-old. Significant differences had P<.05 or less. As expected, SL rats had hyperphagia, higher body weight and higher visceral fat mass at weaning and adulthood. In liver, postnatal EO programmed for lower catalase (-42%), superoxide dismutase (-45%) and glutathione peroxidase (-65%) activities. The evaluation of liver injury in adult SL group showed lower nitrite content (-10%), higher liver and plasma malondialdehyde content (+25% and 1.1-fold increase, respectively). No changes of total protein bound carbonyl or Cu/Zn superoxide dismutase protein expression in liver were detected between the groups. Regarding insulin signaling pathway in liver, SL offspring showed lower IRβ (-66%), IRS1 (-50%), phospho-IRS1 (-73%), PI3-K (-30%) and Akt1 (-58%). Indeed, morphological analysis showed that SL rats presented focal areas of inflammatory cell infiltrate and lipid drops in their cytoplasm characterizing a microsteatosis. Thus, we evidenced that postnatal EO can program the oxidative stress in liver, maybe contributing for impairment of the insulin signaling.
The Journal of nutritional biochemistry 07/2012; · 4.29 Impact Factor