Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice

Renato Chaves Souto Branco, Rafael Ludemann Camargo, Thiago Martins Batista, Jean Franciesco Vettorazzi, Camila Lubaczeuski, Lucas Henrique Montes Bomfim, Leonardo Reis Silveira, Antônio Carlos Boschero, Cláudio Cesar Zoppi, Everardo Magalhães Carneiro

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.

Original languageEnglish (US)
Pages (from-to)6313-6323
Number of pages11
JournalJournal of Cellular Physiology
Issue number5
StatePublished - May 2019
Externally publishedYes


  • fat-enriched diet
  • gastrocnemius
  • insulin sensitivity
  • protein restriction

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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