title: Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.
abstract: 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 d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; 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 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv 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 or 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 d), 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.
authors.affiliation: Neuroendocrine Unit, Instituto Multidisciplinario de Biología Celular, (Consejo Nacional de Investigaciones Científicas y Técnicas-Comisión de Investigaciones Científicas de la Prov. de Buenos Aires), 1900 La Plata, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Alzamendi
authors.forename: Daniel
authors.initials: D
authors.lastname: Castrogiovanni
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Eduardo
authors.initials: E
authors.lastname: Spinedi
authors.forename: Andrés
authors.initials: A
authors.lastname: Giovambattista
mesh_terms: D054392:Adipokines / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D005632:Fructose / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000503:physiopathology*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000503:physiopathology*; D050177:Overweight / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D054392:Adipokines; D004040:Dietary Carbohydrates; D020738:Leptin; D050796:STAT3 Transcription Factor; D005632:Fructose