Increased male offspring’s risk of metabolic-neuroendocrine dysfunction and overweight after fructose rich diet intake by the lactating mother

ALZAMENDI A; CASTROGIOVANNI D; GAILLARD RC; SPINEDI E; GIOVAMBATTISTA A

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2010 vol. 151 p. 4214 - 4223

0013-7227

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal day 1, ad libitum eating, lactating Sprague-Dawley rats received either 10 % F (w/v; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 days of age). Basal circulating levels of metabolic markers were evaluated. Both i.v. glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis, digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 days) and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.