Maternal low-protein diet during lactation combined with early overfeeding impair male offspring's long-term glucose homeostasis.
PURPOSE
The early-life nutritional environment affects long-term glucose homeostasis, we investigated the effects of maternal low-protein diet combined with postnatal early overfeeding on the male offspring's glucose homeostasis in adulthood.


METHODS
Only male rats were used, and their delivery was considered postnatal-day 0 (PN0). Wistar rats' dams were divided into control (NP) or low-protein diet (LP). LP dams remained on the diet until PN14, after which all animals were supplied with the control diet. At PN2, litters were adjusted to 9 (control-NL) or 3 (postnatal-overfeeding-PO) pups, resulting in four experimental groups: NP-NL, NP-PO, LP-NL, and LP-PO. Litters were weaned on PN21. At PN80, a batch of animals from all experimental groups underwent surgery for cannula implantation, followed by intravenous glucose tolerance test (ivGTT), but the insulinogenic index (ISI) was calculated. At PN81, animals were euthanized and tissues were collected.


RESULTS
LP-diet and early postnatal-overfeeding were effective in promoting the expected biometric outcomes at PN21 and PN81, but the LP-PO animals present a biometric profile similar to the control (NP-NL) group. Postnatal-overfeeding increased fasting glycemia in LP-PO animals (p < 0.01). In the ivGTT, postnatal-overfeeding elevated the glycemia (p < 0.0001), exacerbated in LP-PO animals (p < 0.0001). Insulinemia was reduced by both, maternal LP-diet and postnatal-overfeeding, with a higher degree of reduction in LP-PO animals (p < 0.0001). Maternal LP-diet and postnatal-overfeeding reduced the ISI (p < 0.0001). Factors interaction lead the LP-PO to a lower ISI compared to all other groups (p < 0.0001).


CONCLUSIONS
The combination of low-protein diet in breastfeeding dams with postnatal overfeeding disturbed the offspring's glucose metabolism in adulthood.
['Almeida|Douglas Lopes|DL|http://orcid.org/0000-0002-1596-9821', 'Simões|Fernando Salgueiro|FS|', 'Saavedra|Lucas Paulo Jacinto|LPJ|', 'Praxedes Moraes|Ana Maria|AM|', 'Matiusso|Camila Cristina Ianoni|CCI|', 'Malta|Ananda|A|', 'Palma-Rigo|Kesia|K|', 'Mathias|Paulo Cesar de Freitas|PCF|']
D000818:Animals D000831:Animals, Newborn D001786:Blood Glucose D018753:Diet, Protein-Restricted D004435:Eating D005260:Female D005951:Glucose Tolerance Test D006706:Homeostasis D006963:Hyperphagia D007328:Insulin D007774:Lactation D008297:Male D039382:Maternal Nutritional Physiological Phenomena D051381:Rats D017208:Rats, Wistar
Glucose homeostasis DOHaD Early postnatal overfeeding Maternal diet Metabolic programming