Perinatal factors are likely to be involved in the problem of centralization of body fat stores. This idea originates from studies by Barker (25), who found that children born small for gestational age frequently develop centralization of body fat and associated metabolic syndrome, 'the small baby syndrome'. Although originally based on statistical observations from populations where intrauterine undernutrition was suspected, this hypothesis has gained considerable support from the results of recent studies.
Subjects with the small baby syndrome and abdominal preponderance of body fat stores have recently been reported to have elevated cortisol secretion (26). This might correspond to the group of men we have studied with elevated stress-related cortisol and centralization of body fat (8,17).
There are experimental studies which indicate potential mechanisms. The HPA axis can be sensitized by intrauterine exposure to immune stress or cytokine exposure or to lipopolysaccharides (27,28), and the handling of newborns has also been shown to be of importance (29). Recent studies have provided further interesting information, probably explaining the effects of prenatal exposure to lipo-polysaccharides. These bacterial endotoxins stimulate the secretion of cytokines. Prenatal exposure to interleukin-6, tumour necrosis factor a or dex-amethasone, a synthetic glucocorticoid which passes the placental barrier, is followed by permanent sensitization of the HPA axis, leptin-resistant obesity and insulin resistance (30). It seems likely that leptin-resistant obesity is caused by the increased corticosterone secretion from the HPA axis, because a similar condition develops after elevated corticosterone exposure in adult rats (31). This is probably applicable also to humans because it is well known from clinical experience that patients treated with glucocorticoids overeat and become obese. Furthermore, in recent experiments we have been able to show that women taking 25 mg pred-nisolone daily for a week increase their food intake in spite of elevated leptin concentrations (32).
These interesting developments suggest that centralization of body fat and also the development of obesity might be affected not only by Cortisol in adulthood, but also by prenatal factors. Infections during pregnancy might speculatively be involved in such developments.
It is thus apparent that perinatal factors are critical for the development of obesity and centralization of body fat stores with its metabolic associates in adult life. Evidence suggests that this might at least partly be mediated via programming of the regulation of the HPA axis. It will be of interest in the future to find out to what extent 'the small baby syndrome' is involved in the overall prevalence of centralization of body fat and the metabolic syndrome in adult life.
parallel activation of the HPA axis and the sympathetic nervous system at central levels. It seems likely that the sympathetic nervous system is responsible for blood pressure elevation and the HPA axis for insulin resistance with hyperinsulinaemia following as described above. The HPA axis is presumably also responsible for the centralization of body fat as also discussed above.
In the case of primary hypertension; centralization of body fat stores seems to be a sign of central neuroendocrine disturbances where elevated blood pressure is probably due to a parallel activation of the sympathetic nervous system, also occurring at a central level. It may well be, however, that insulin amplifies this autonomic activation. For further discussion of this problem, see review in Bjorntorp et al. (35).
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