Data from: Urinary signatures are associated with calorie restriction-mediated weight loss in obese Diversity Outbred mice

Metabolomic profiles are increasingly being used to identify responders to
dietary interventions. Advances using this approach are particularly
needed to personalize and enhance the effectiveness of dietary weight loss
interventions. Using obese Diversity Outbred (DO) mice that model genetic
and phenotypic heterogeneity of human populations, we aimed to identify
urinary metabolite signatures associated with responsiveness to calorie
restriction (CR)-mediated weight loss. DO mice (150 males, 150 females)
were fed a high-fat diet for 12 weeks to induce obesity, then urine was
collected and an 8-week CR regimen (30 % decrease in energy intake)
initiated. At study completion, mice were rank-ordered according to their
percent body weight change, with mice in the extreme quartiles deemed CR
responders (n = 67) versus nonresponders (n = 67). Targeted
semi-quantitative metabolomics identified elevated glutamic acid and
hydroxyproline as key urinary metabolites that distinguish CR responders
from CR nonresponders, independent of sex. Three urinary metabolites
(glutamic acid, hydroxyproline, and putrescine) distinguished male CR
responders from nonresponders. Six metabolites (glutamic acid,
hydroxyproline, dopamine, histamine, lysine, and spermine) distinguished
female CR responders from nonresponders. Multivariate receiver operating
characteristic analyses integrated these metabolites to reveal potential
sex specific and sex-independent associations of CR-mediated weight loss.
Further, pathway analysis identified several metabolic pathways, including
arginine and proline metabolism, and alanine, aspartate, and glutamate
biosynthesis, that distinguished CR responders from nonresponders and
could be indicative of metabolic reprogramming to enhance insulin
sensitivity and energy metabolism.