Abstract
Adjustment of protein content in milk formulations modifies protein and energy levels, ensures amino acid intake and affects satiety. The shift from the natural whey:casein ratio of ~20:80 in animal milk is oftentimes done to reflect the 60:40 ratio of human milk. Studies show that 20:80 versus 60:40 whey:casein milks differently affect glucose metabolism and hormone release; these data parallel animal model findings. It is unknown whether the adjustment from the 20:80 to 60:40 ratio affects appetite and brain processes related to food intake. In this set of studies, we focused on the impact of the 20:80 vs. 60:40 whey:casein content in milk on food intake and feeding-related brain processes in the adult organism. By utilising laboratory mice, we found that the 20:80 whey:casein milk formulation was consumed less avidly and was less preferred than the 60:40 formulation in short-term choice and no-choice feeding paradigms. The relative PCR analyses in the hypothalamus and brain stem revealed that the 20:80 whey:casein milk intake upregulated genes involved in early termination of feeding and in an interplay between reward and satiety, such as melanocortin 3 receptor (MC3R), oxytocin (OXT), proopiomelanocortin (POMC) and glucagon-like peptide-1 receptor (GLP1R). The 20:80 versus 60:40 whey:casein formulation intake differently affected brain neuronal activation (assessed through c-Fos, an immediate-early gene product) in the nucleus of the solitary tract, area postrema, ventromedial hypothalamic nucleus and supraoptic nucleus. We conclude that the shift from the 20:80 to 60:40 whey:casein ratio in milk affects short-term feeding and relevant brain processes.
Highlights
Unlike the 60:40 whey:casein ratio of human milk, the protein fraction of animal milks has the natural whey:casein ratio of approximately 20:80 [6]; and milk formulations used in human nutrition—most commonly infant formulas—are often whey-enhanced to match the 60:40 ratio [7,8,9]
The comparison with the group that received water instead of a milk formulation revealed that both formulations were preferred over water (F(2,27) = 3.779); water vs. Control 20:80–p = 0.034; water vs. 60:40–p < 0.001)
Chow intake was lower in the milk groups than in water-given mice, showing a strong trend approaching significance
Summary
Milk proteins consist primarily of whey and casein [5]. It is well established that proteins, including those present in milk, affect appetite, body weight and metabolic parameters [1,5,10]. Data showed that whey and casein generate distinct physiological and appetitive responses by interacting with specific transporters and receptors in the gut, affecting nutrient absorption, modifying gastric emptying and gastrointestinal (GI) hormone release [1,5,11,12]. Whey and casein have unique digestion kinetics and post-absorptive effects. Digestion of whey is rapid compared to casein: casein proteins aggregate into curds [13,14], delaying delivery of constituent metabolites to the intestine [11,15,16,17]. Plasma amino acid levels reflect digestion speed, with whey intake inducing higher, immediate increases in circulating amino acids [11,18,19]
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