Overweight and Metabolic and Hormonal Parameter Disruption Are Induced in Adult Male Mice by Manipulations During Lactation Period

Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Roma, Italy.
Pediatric Research (Impact Factor: 2.31). 02/2006; 59(1):111-5. DOI: 10.1203/01.pdr.0000190575.12965.ce
Source: PubMed


Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features.

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Available from: Giuseppe Seghieri, May 13, 2014
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    • "Limited data from animal studies have found that stress caused by handling during the neonatal period may also be detrimental. Studies have found that neonatal mice, which were under maternal separation plus subcutaneous sham injection during the lactation period, developed hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia in adult under fasting [110, 111]. Increased plasma corticosterone and adrenocorticotropin were found in these animals [110, 111] which might be responsible for the “diabetic” alteration. "
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    • "Stress-induced increase in maternal plasma corticosterone is associated with altered anxiety traits in adult male offspring, and also in cross-fostered male offspring (Bartolomucci et al., 2004; Moles et al., 2004; Moles et al., 2008). Similar to the observed phenotype in fostered mice, early postnatal exposure to exogenous glucocotricods in rodents also leads to increased body weight in adulthood (Gonzalez et al., 1990; Loizzo et al., 2006) and increased hepatic triglyceride content (Liu et al., 2007). A detailed profiling of the maternal and neonatal stress axes in response to fostering is beyond the scope of this study, but extensive temporal profiling of glucocorticoids would be required to establish the role of the Hypothalamic Pituitary Adrenal (HPA) axis. "
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    • "There is a lot of discrepancy in literature regarding stress and bodyweight changes. Indeed, both increases and decreases in bodyweight gain have been described, not only following early-life stress but also other types of stressors (Loizzo et al., 2006; Krishnan et al., 2007; Veenema et al., 2008; Savignac et al., 2011). Together, these data suggest that bodyweight alterations induced by stress are under complex regulatory processes and may depend on the nature and context of stress. "
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