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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; · 2.19 Impact Factor
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P A Trotta,
E G Moura,
J G Franco,
N S Lima, E de Oliveira,
A Cordeiro,
L L Souza,
K J Oliveira,
P C Lisboa,
C C Pazos Moura,
M C F Passos
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ABSTRACT: 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.
Hormone and Metabolic Research 02/2011; 43(3):171-7. · 2.19 Impact Factor
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ABSTRACT: 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.
Hormone and Metabolic Research 05/2010; 42(8):562-9. · 2.19 Impact Factor
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ABSTRACT: 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.
Hormone and Metabolic Research 09/2009; 41(12):866-73. · 2.19 Impact Factor
