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A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation
Amelia Palermo1,2,3,4, Shen Li5,6,7,8,9,10, Johanna Ten Hoeve2,3,4
1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Abstract:
The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.
Insights
The ketogenic diet (KD) improved survival and reduced inflammation in mice infected with SARS-CoV-2. This dietary intervention mitigated systemic toxicity and restored metabolic balance, offering potential therapeutic insights.
Area of Science:
- Immunology
- Virology
- Metabolic Medicine
Background:
- The ketogenic diet (KD) is known for its anti-inflammatory properties.
- SARS-CoV-2 infection causes significant systemic toxicity and immune dysregulation.
Purpose of the Study:
- To investigate the impact of a KD on systemic toxicity in mice during SARS-CoV-2 infection.
- To assess the KD's effects on immune response, inflammation, and metabolic changes post-infection.
Main Methods:
- Mice were infected with SARS-CoV-2 and treated with a KD.
- Systemic toxicity, survival rates, and multi-organ transcriptional and metabolic profiles were analyzed.
- Serum cytokine levels, inflammatory markers, and metabolite ratios were measured.
Main Results:
- KD significantly improved survival and reduced weight loss in infected mice.
- KD mitigated multi-organ transcriptional reprogramming and metabolic rewiring induced by SARS-CoV-2.
- Reduced pro-inflammatory cytokines, inflammatory prostaglandins, and kynurenine/tryptophan ratio were observed, indicating decreased systemic inflammation.
Conclusions:
- The ketogenic diet alters the host response to SARS-CoV-2 infection.
- KD improves health outcomes by reducing inflammation and restoring metabolic homeostasis in infected mice.
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