Mitochondrial dysfunction may be a long-term consequence to poor nutritional environment during early life. Our aim was to investigate whether maternal low protein 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 (C) or 8% protein (LP) throughout gestation. From birth, offspring received the control diet. The mitochondrial function was analyzed in islets of 3 month-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 to C offspring. The expression of malate deshydrogenase 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 to C. Several consequences of protein restriction during fetal life were more marked in male offspring. Only LP males showed an increased ROS production associated to a higher expression of mitochondrial subunits of the electron transport chain ND4L, an overexpression of PPARgamma and UCP-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 a LP diet. Key words: Developmental programming, Islets, Low protein diet, mitochondria.
Theys, N., Bouckenooghe, T., Ahn, M.-T., Remacle, C., & Reusens, B. (2009). Maternal low protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat. American journal of physiology. Regulatory, integrative and comparative physiology, 297(5), R1516-25. https://doi.org/10.1152/ajpregu.00280.2009 (Original work published 2009)