Metabolomics Insights into the Modulatory Effects of Long-Term Low Calorie Intake in Mice.
There is increasing evidence that calorie restriction without malnutrition can extend longevity and delay the onset of age-associated disorders. Identifying the biochemical perturbations associated with different dietary habits would provide valuable insights into associations between metabolism and longevity. To reveal the effects of long-term dietary interventions on metabolic perturbations, we investigated serum and urinary metabolic changes induced by interactive high/low fat diet in combination with/without reduced caloric intake over a life span in mice using NMR-based metabonomics. We found that the high calorie dietary regime disturbed lipid metabolism, suppressed glycolysis and TCA cycles, stimulated oxidative stress, promoted nucleotide metabolism and gluconeogenesis, and perturbed gut microbiota-host interactions. Such changes could be modified by long-term low calorie intake. Most importantly, we found that the calorie intake index exerts a dominant effect on metabolic perturbations irrespective of dietary regime. Our investigation provides a holistic view of the metabolic impact of long-term dietary interventions, which are important for detecting physiological changes and dietary effects on mammalian metabolism.
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, P. R. China.
Junfang
J
Wu
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, P. R. China.
Liu
L
Yang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, P. R. China.
Shoufeng
S
Li
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, P. R. China.
Ping
P
Huang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, P. R. China.
Yong
Y
Liu
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, P. R. China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University , Hangzhou 310058, P. R. China.
Yulan
Y
Wang
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, P. R. China.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Metabolomics and Systems Biology Laboratory, School of Life Sciences, Fudan University , Shanghai 200433, P. R. China.
Huiru
H
Tang
D000818:Animals; D031204:Caloric Restriction; D059305:Diet, High-Fat / Q000009:adverse effects; D002149:Energy Intake / Q000502:physiology*; D008136:Longevity; D009682:Magnetic Resonance Spectroscopy; D008660:Metabolism / Q000502:physiology; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D044967:Serum / Q000378:metabolism; D014556:Urine / Q000737:chemistry
NMR; calorie restriction; high fat diet; long-term diet interventions; metabonomics