The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice
| Autor: | Rahul Gokarn, David Raubenheimer, Samantha M. Solon-Biet, Xin Huang, David A. Sinclair, Kari Ruohonen, Aisling C. McMahon, Lindsay E. Wu, Victoria C. Cogger, J. William O. Ballard, Stephen J. Simpson, Nicolas Pichaud, Gregory J. Cooney, Richard G. Melvin, Nigel Turner, Alessandra Warren, Mamdouh Khalil, David G. Le Couteur |
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| Rok vydání: | 2013 |
| Předmět: |
Leptin
Male medicine.medical_specialty Aging Physiology medicine.medical_treatment media_common.quotation_subject Calorie restriction Longevity Blood Pressure Kaplan-Meier Estimate Biology Article Cardiovascular Physiological Phenomena 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Glucose Intolerance medicine Animals Insulin Phosphorylation Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology media_common 2. Zero hunger 0303 health sciences TOR Serine-Threonine Kinases Cell Biology Carbohydrate Caloric intake Diet Mice Inbred C57BL Human nutrition Endocrinology Cell metabolism Glucose Liver Body Composition Energy Intake 030217 neurology & neurosurgery Amino Acids Branched-Chain |
| Zdroj: | Cell metabolism. 19(3) |
| ISSN: | 1932-7420 |
| Popis: | SummaryThe fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. |
| Databáze: | OpenAIRE |
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