We examined the long-term effects of protein restriction during puberty on the function of hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes in male rats. Male Wistar rats from the age of 30 to 60 days were fed a low-protein diet (4%, LP). A normal-protein diet (20.5%) was reintroduced to rats from the age of 60 to 120 days. Control rats were fed a normal-protein diet throughout life (NP). Rats of 60 or 120 days old were killed. Food consumption, body weight, visceral fat deposits, lipid profile, glycemia, insulinemia, corticosteronemia, adrenocorticotropic hormone (ACTH), testosteronemia and leptinemia were evaluated. Glucose-insulin homeostasis, pancreatic-islet insulinotropic response, testosterone production and hypothalamic protein expression of the androgen receptor (AR), glucocorticoid receptor (GR) and leptin signaling pathway were also determined. LP rats were hypophagic, leaner, hypoglycemic, hypoinsulinemic and hypoleptinemic at the age of 60 days (P < 0.05). These rats exhibited hyperactivity of the HPA axis, hypoactivity of the HPG axis and a weak insulinotropic response (P < 0.01). LP rats at the age of 120 days were hyperphagic and exhibited higher visceral fat accumulation, hyperleptinemia and dyslipidemia; lower blood ACTH, testosterone and testosterone release; and reduced hypothalamic expression of AR, GR and SOCS3, with a higher pSTAT3/STAT3 ratio (P < 0.05). Glucose-insulin homeostasis was disrupted and associated with hyperglycemia, hyperinsulinemia and increased insulinotropic response of the pancreatic islets. The cholinergic and glucose pancreatic-islet responses were small in 60-day-old LP rats but increased in 120-day-old LP rats. The hyperactivity of the HPA axis and the suppression of the HPG axis caused by protein restriction at puberty contributed to energy and metabolic disorders as long-term consequences.
Júlio Cezar de Oliveira, Egberto Gaspar de Moura, Rosiane Aparecida Miranda, Ana Maria Praxedes de Moraes, Luiz Felipe Barella, Ellen Paula Santos da Conceição, Rodrigo Mello Gomes, Tatiane Aparecida Ribeiro, Ananda Malta, Isabela Peixoto Martins, Claudinéia Conationi da Silva Franco, Patrícia Cristina Lisboa, and Paulo Cezar de Freitas Mathias
Tatiane Aparecida Ribeiro, Audrei Pavanello, Laize Peron Tófolo, Júlio Cezar de Oliveira, Ana Maria Praxedes de Moraes, Claudinéia Conationi da Silva Franco, Kelly Valério Prates, Isabela Peixoto Martins, Kesia Palma-Rigo, Rosana Torrezan, Erica Yeo, Rodrigo Mello Gomes, Flávio Andrade Francisco, Paulo Cezar de Freitas Mathias, and Ananda Malta
We tested whether chronic supplementation with soy isoflavones could modulate insulin secretion levels and subsequent recovery of pancreatic islet function as well as prevent metabolic dysfunction induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) were used as models of early overfeeding and normal feeding, respectively. At 30 to 90 days old, animals in the SL and NL groups received either soy isoflavones extract (ISO) or water (W) gavage serving as controls. At 90 days old, body weight, visceral fat deposits, glycemia, insulinemia were evaluated. Glucose-insulin homeostasis and pancreatic-islet insulinotropic response were also determined.
The early life overnutrition induced by small litter displayed metabolic dysfunction, glucose and insulin homeostasis disruption in adult rats. However, adult SL rats treated with soy isoflavones showed improvement in glucose tolerance, insulin sensitivity, insulinemia, fat tissue accretion and body weight gain, compared with SL-W group. Pancreatic-islet response to cholinergic, adrenergic and glucose stimuli was improved in both isoflavone-treated groups. In addition, different isoflavone concentrations increased glucose-stimulated insulin secretion in islets of all groups with higher magnitude in both NL and SL isoflavone treated groups. These results indicate that long-term treatment with soy isoflavones inhibits early overfeeding-induced metabolic dysfunction in adult rats and modulated the process of insulin secretion in pancreatic islets.