Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation
- PMID: 19549860
- PMCID: PMC2700149
- DOI: 10.1073/pnas.0902366106
Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation
Abstract
Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of the diet when these components are plentiful. Here we examine how the microbiota shapes host metabolic and physiologic adaptations to periods of nutrient deprivation. Germ-free (GF) mice and mice who had received a gut microbiota transplant from conventionally raised donors were compared in the fed and fasted states by using functional genomic, biochemical, and physiologic assays. A 24-h fast produces a marked change in gut microbial ecology. Short-chain fatty acids generated from microbial fermentation of available glycans are maintained at higher levels compared with GF controls. During fasting, a microbiota-dependent, Ppar alpha-regulated increase in hepatic ketogenesis occurs, and myocardial metabolism is directed to ketone body utilization. Analyses of heart rate, hydraulic work, and output, mitochondrial morphology, number, and respiration, plus ketone body, fatty acid, and glucose oxidation in isolated perfused working hearts from GF and colonized animals (combined with in vivo assessments of myocardial physiology) revealed that the fasted GF heart is able to sustain its performance by increasing glucose utilization, but heart weight, measured echocardiographically or as wet mass and normalized to tibial length or lean body weight, is significantly reduced in both fasted and fed mice. This myocardial-mass phenotype is completely reversed in GF mice by consumption of a ketogenic diet. Together, these results illustrate benefits provided by the gut microbiota during periods of nutrient deprivation, and emphasize the importance of further exploring the relationship between gut microbes and cardiovascular health.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2708699/bin/zpq9990985880001.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2708699/bin/zpq9990985880002.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2708699/bin/zpq9990985880003.gif)
Similar articles
-
Blood flow and nutrient exchange across the liver and gut of the dairy cow. Effects of lactation and fasting.Br J Nutr. 1983 May;49(3):481-96. doi: 10.1079/bjn19830057. Br J Nutr. 1983. PMID: 6860627
-
Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice.Gastroenterology. 2013 May;144(5):967-77. doi: 10.1053/j.gastro.2013.01.047. Epub 2013 Feb 1. Gastroenterology. 2013. PMID: 23380084 Free PMC article.
-
Cardiac metabolic modulation upon low-carbohydrate low-protein ketogenic diet in diabetic rats studied in vivo using hyperpolarized 13 C pyruvate, butyrate and acetoacetate probes.Diabetes Obes Metab. 2019 Apr;21(4):949-960. doi: 10.1111/dom.13608. Epub 2019 Jan 13. Diabetes Obes Metab. 2019. PMID: 30536560
-
Ketone body metabolism and cardiovascular disease.Am J Physiol Heart Circ Physiol. 2013 Apr 15;304(8):H1060-76. doi: 10.1152/ajpheart.00646.2012. Epub 2013 Feb 8. Am J Physiol Heart Circ Physiol. 2013. PMID: 23396451 Free PMC article. Review.
-
Role of ketone bodies in perinatal myocardial energy metabolism.Biochem Soc Trans. 2001 May;29(Pt 2):325-30. doi: 10.1042/0300-5127:0290325. Biochem Soc Trans. 2001. PMID: 11356176 Review.
Cited by
-
Nutritional Considerations During Major Weight Loss Therapy: Focus on Optimal Protein and a Low-Carbohydrate Dietary Pattern.Curr Nutr Rep. 2024 Sep;13(3):422-443. doi: 10.1007/s13668-024-00548-6. Epub 2024 May 30. Curr Nutr Rep. 2024. PMID: 38814519 Free PMC article. Review.
-
Deciphering the Role of the Gut Microbiota in Exposure to Emerging Contaminants and Diabetes: A Review.Metabolites. 2024 Feb 6;14(2):108. doi: 10.3390/metabo14020108. Metabolites. 2024. PMID: 38393000 Free PMC article. Review.
-
Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.Toxics. 2024 Jan 8;12(1):47. doi: 10.3390/toxics12010047. Toxics. 2024. PMID: 38251002 Free PMC article. Review.
-
Seasonal Variations in Production Performance, Health Status, and Gut Microbiota of Meat Rabbit Reared in Semi-Confined Conditions.Animals (Basel). 2023 Dec 28;14(1):113. doi: 10.3390/ani14010113. Animals (Basel). 2023. PMID: 38200844 Free PMC article.
-
Gut butyrate-producers confer post-infarction cardiac protection.Nat Commun. 2023 Nov 9;14(1):7249. doi: 10.1038/s41467-023-43167-5. Nat Commun. 2023. PMID: 37945565 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
- R01 DK070977/DK/NIDDK NIH HHS/United States
- DK052574/DK/NIDDK NIH HHS/United States
- T32 GM065103-07/GM/NIGMS NIH HHS/United States
- P30 DK056341-06/DK/NIDDK NIH HHS/United States
- DK70977/DK/NIDDK NIH HHS/United States
- P30 DK020579/DK/NIDDK NIH HHS/United States
- P30 DK052574/DK/NIDDK NIH HHS/United States
- DK020579/DK/NIDDK NIH HHS/United States
- P30 DK056341/DK/NIDDK NIH HHS/United States
- P30 DK056341-07/DK/NIDDK NIH HHS/United States
- P60 DK020579/DK/NIDDK NIH HHS/United States
- DK073282/DK/NIDDK NIH HHS/United States
- T32 GM065103/GM/NIGMS NIH HHS/United States
- DK56341/DK/NIDDK NIH HHS/United States
- K08 DK073282/DK/NIDDK NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources