Implementation of dietary methionine restriction using casein after selective, oxidative deletion of methionine

Han Fang; Kirsten P Stone; Laura A Forney; Landon C Sims; Gabriela C Gutierrez; Sujoy Ghosh; Thomas W Gettys

doi:10.1016/j.isci.2021.102470

Implementation of dietary methionine restriction using casein after selective, oxidative deletion of methionine

iScience. 2021 Apr 24;24(5):102470. doi: 10.1016/j.isci.2021.102470. eCollection 2021 May 21.

Authors

Han Fang¹, Kirsten P Stone¹, Laura A Forney^{1

2}, Landon C Sims¹, Gabriela C Gutierrez³, Sujoy Ghosh^{4

5}, Thomas W Gettys¹

Affiliations

¹ Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
² Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
³ School of Nutrition and Food Sciences, Louisiana State University, Baton Rouge, LA 70809, USA.
⁴ Laboratory of Computational Biology, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
⁵ Program in Cardiovascular and Metabolic Disorders and Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore.

Abstract

Dietary methionine restriction (MR) is normally implemented using diets formulated from elemental amino acids (AA) that reduce methionine content to ∼0.17%. However, translational implementation of MR with elemental AA-based diets is intractable due to poor palatability. To solve this problem and restrict methionine using intact proteins, casein was subjected to mild oxidation to selectively reduce methionine. Diets were then formulated using oxidized casein, adding back methionine to produce a final concentration of 0.17%. The biological efficacy of dietary MR using the oxidized casein (Ox Cas) diet was compared with the standard elemental MR diet in terms of the behavioral, metabolic, endocrine, and transcriptional responses to the four diets. The Ox Cas MR diet faithfully reproduced the expected physiological, biochemical, and transcriptional responses in liver and inguinal white adipose tissue. Collectively, these findings demonstrate that dietary MR can be effectively implemented using casein after selective oxidative reduction of methionine.

Keywords: Diet; Metabolic engineering; Nutrition.

Abstract

Grants and funding