Body weight loss, effective satiation and absence of homeostatic neuropeptide compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet

Appetite. 2017 Oct 1:117:234-246. doi: 10.1016/j.appet.2017.06.029. Epub 2017 Jul 5.


Food structure contributes to the induction of satiation and the maintenance of satiety following intake of a meal. There is evidence from human studies that protein-crosslinking of a milk-protein based meal may enhance satiety, but the mechanism underpinning this effect is unknown. We investigated whether a rat model would respond in a similar manner and might provide mechanistic insight into enhanced satiety by structural modification of a food source. Rats were schedule fed a modified AIN-93M based diet in a liquid form or protein-crosslinked to produce a soft-solid form. This was compared to a modified AIN-93M solid diet. Average daily caloric intake was in the order solid > liquid > crosslinked. Body composition was unaltered in the solid group, but there was a loss of fat in the liquid group and a loss of lean and fat tissue in the crosslinked group. Compared to rats fed a solid diet, acute responses in circulating GLP-1, leptin and insulin were eliminated or attenuated in rats fed a liquid or crosslinked diet. Quantification of homeostatic neuropeptide expression in the hypothalamus showed elevated levels of Npy and Agrp in rats fed the liquid diet. Measurement of food intake after a scheduled meal indicated that reduced energy intake of liquid and crosslinked diets is not due to enhancement of satiety. When continuously available ad-libitum, rats fed a liquid diet showed reduced weight gain despite greater 24 h caloric intake. During the dark phase, caloric intake was reduced, but compensated for during the light phase. We conclude that structural modification from a liquid to a solidified state is beneficial for satiation, with less of a detrimental effect on metabolic parameters and homeostatic neuropeptides.

Keywords: Food reformulation; Satiation; Satiety; Transglutaminase.

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Animals
  • Diet, Reducing*
  • Energy Intake*
  • Food Handling
  • Gene Expression Regulation
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism
  • Hypothalamus / metabolism*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Leptin / blood
  • Leptin / metabolism
  • Male
  • Milk Proteins / administration & dosage*
  • Milk Proteins / adverse effects
  • Milk Proteins / chemistry
  • Milk Proteins / metabolism
  • Neurons / metabolism*
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism
  • Overweight / blood
  • Overweight / diet therapy
  • Overweight / metabolism
  • Overweight / prevention & control
  • Rats, Sprague-Dawley
  • Satiety Response*
  • Transglutaminases / metabolism*
  • Weight Gain
  • Weight Loss


  • AGRP protein, rat
  • Agouti-Related Protein
  • Insulin
  • Leptin
  • Milk Proteins
  • Neuropeptide Y
  • Glucagon-Like Peptide 1
  • Transglutaminases