Mice Regulate Dietary Amino Acid Balance and Energy Intake by Selecting between Complementary Protein Sources

Kamrul Zaman; Hee-Chang Mun; Samantha M Solon-Biet; Alistair M Senior; David Raubenheimer; Stephen J Simpson; Arthur D Conigrave

doi:10.1016/j.tjnut.2024.04.007

Mice Regulate Dietary Amino Acid Balance and Energy Intake by Selecting between Complementary Protein Sources

J Nutr. 2024 Apr 5:S0022-3166(24)00172-X. doi: 10.1016/j.tjnut.2024.04.007. Online ahead of print.

Authors

Kamrul Zaman¹, Hee-Chang Mun¹, Samantha M Solon-Biet¹, Alistair M Senior¹, David Raubenheimer¹, Stephen J Simpson¹, Arthur D Conigrave²

Affiliations

¹ Charles Perkins Centre and School of Life & Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
² Charles Perkins Centre and School of Life & Environmental Sciences, University of Sydney, Sydney, NSW, Australia. Electronic address: arthur.conigrave@sydney.edu.au.

PMID: 38583524
DOI: 10.1016/j.tjnut.2024.04.007

Abstract

Background: A balanced intake of protein and constituent amino acids (AAs) requires adjustments to total food intake (protein leverage [PL]) and food selection to balance deficits and excesses (complementary feeding). We provided mice with choices of casein and whey, 2 protein sources that are complementary in AA balance, across a range of protein concentrations (P%) of digestible energy (DE).

Objectives: We aimed to determine if: 1) PL operates similarly for casein and whey; 2) one protein source is preferred at control P%; 3) the preference changes as P% falls; and 4) AA intakes under control and low P% levels identify AAs that drive changes in protein selection.

Methods: Food intake and plasma fibroblast growth factor-21 (FGF21) concentrations were measured in mice at various P% (P7.5%-P33%). For direct comparisons, defined diets were used in which the protein source was either casein or whey. In food choice studies, mice had access to foods in which both casein and whey were provided at the same P% level at the same time.

Results: PL operated at different P% thresholds in casein (13%)- and whey (10%)-based diets, and the magnitude of PL was greater for casein. Although mice preferred casein under control conditions (P23%), a pronounced preference shift to whey occurred as P% fell to P13% and P10%. At low P%, increases in food intake were accompanied by increases in plasma FGF21, a protein hunger signal. Among AAs deficient in casein and enriched in whey, the intake of Cys was the most invariant as P% changed between P23% and P10%, appearing to drive the switch in protein preference.

Conclusions: Mice selected between complementary protein sources, casein and whey, achieving stable total energy intake and regulated intake of AAs as P% varied. Supplementation of low P% casein diets with one whey-enriched AA, Cys, suppressed plasma FGF21 and total food intake.

Keywords: amino acids; dietary protein selection; food intake; milk proteins; protein leverage.