Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat.
Am J Physiol Regul Integr Comp Physiol
; 297(5): R1516-25, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19759337
ABSTRACT
Mitochondrial dysfunction may be a long-term consequence of a poor nutritional environment during early life. Our aim was to investigate whether a maternal low-protein (LP) diet may program mitochondrial dysfunction in islets of adult progeny before glucose intolerance ensues. To address this, pregnant Wistar rats were fed isocaloric diets containing either 20% protein (control) or 8% protein (LP diet) throughout gestation. From birth, offspring received the control diet. The mitochondrial function was analyzed in islets of 3-mo-old offspring. Related to their basal insulin release, cultured islets from both male and female LP offspring presented a lower response to glucose challenge and a blunted ATP production compared with control offspring. The expression of malate dehydrogenase as well as the subunit 6 of the ATP synthase encoded by mitochondrial genome (mtDNA) was lower in these islets, reducing the capacity of ATP production through the Krebs cycle and oxidative phosphorylation. However, mtDNA content was unchanged in LP islets compared with control. Several consequences of protein restriction during fetal life were more marked in male offspring. Only LP males showed an increased reactive oxygen species production associated with a higher expression of mitochondrial subunits of the electron transport chain NADH-ubiquinone oxireductase subunit 4L, an overexpression of peroxisome proliferator-activated receptor-gamma and uncoupling protein-2, and a strongly reduced beta-cell mass. In conclusion, mitochondrial function is clearly altered in islets from LP adult offspring in a sex-specific manner. That may provide a cellular explanation for the earlier development of glucose intolerance in male than in female offspring of dams fed an LP diet.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
/
Prenhez
/
Ilhotas Pancreáticas
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Caracteres Sexuais
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Dieta com Restrição de Proteínas
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Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Am J Physiol Regul Integr Comp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Bélgica