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Published on: September 12, 2016
High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection
Duan Ni1,2,3,4, Jian Tan1,2, Julen Reyes1,2,3,4
1Charles Perkins Centre, The University of Sydney, D17 Charles Perkins Centre, Sydney, NSW, 2006, Australia.
Abstract:
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) believed to be driven by autoimmune mechanisms. Genetic and environmental factors are implicated in MS development, and among the latter, diets and nutrients are emerging as potential critical contributors. However, a comprehensive understanding of their impacts and the underlying mechanisms involved is lacking. Harnessing state-of-the-art nutritional geometry analytical methods, it is first revealed that globally, increased carbohydrate supply is associated with increased MS disease burden, while fat supply has an opposite effect. Furthermore, in a MS mouse model, experimental autoimmune encephalomyelitis (EAE), it is found that an isocaloric diet high in carbohydrate aggravated EAE, while a diet enriched in fat (HF) is fully protective. This is reflected by reduced neuroinflammation and skewing toward anti-inflammatory phenotypes. The protective effects from the HF diet are multifaceted. Metabolically, HF increased lipid storage in immune cells, correlating with their increased anti-inflammatory IL-10 production. Transcriptionally and epigenetically, HF feeding preprogrammed naïve T cells toward a less activated but more tolerogenic phenotype. It is showcased that manipulating diets is a potentially efficient and cost-effective approach to prevent and/or ameliorate EAE. This exhibits translational potentials for prevention/intervention of MS and possibly other autoimmune diseases.
Insights
Dietary fat intake may protect against multiple sclerosis (MS). A high-fat diet reduced disease severity and inflammation in a mouse model, suggesting potential dietary interventions for MS prevention.
Area of Science:
- Neuroimmunology
- Nutritional Science
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) is an inflammatory and neurodegenerative central nervous system (CNS) disease with suspected autoimmune origins.
- Dietary factors are increasingly recognized as potential contributors to MS development, but mechanisms remain unclear.
- Existing research lacks a comprehensive understanding of diet's impact on MS pathogenesis.
Purpose of the Study:
- To investigate the global association between dietary macronutrient supply and MS disease burden.
- To determine the effects of high-carbohydrate versus high-fat diets on experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
- To elucidate the metabolic, transcriptional, and epigenetic mechanisms underlying the impact of diet on autoimmune responses.
Main Methods:
- Utilized nutritional geometry to analyze global dietary patterns and MS prevalence.
- Employed an experimental autoimmune encephalomyelitis (EAE) mouse model to assess dietary interventions.
- Analyzed immune cell metabolism, lipid storage, cytokine production (IL-10), and T cell phenotypes (transcriptional and epigenetic profiles).
Main Results:
- Global analysis indicated a positive correlation between carbohydrate supply and MS burden, and an inverse relationship with fat supply.
- In the EAE model, a high-fat (HF) diet conferred complete protection, while a high-carbohydrate diet exacerbated disease.
- HF diet reduced neuroinflammation, promoted anti-inflammatory phenotypes, increased lipid storage in immune cells, and induced IL-10 production. It also shifted T cells toward a tolerogenic phenotype.
Conclusions:
- Dietary fat intake, particularly a high-fat diet, demonstrates significant protective effects against experimental autoimmune encephalomyelitis.
- The protective mechanisms involve reduced neuroinflammation, enhanced anti-inflammatory immune cell profiles, and T cell reprogramming.
- Dietary manipulation presents a promising, cost-effective strategy for preventing and managing MS and potentially other autoimmune conditions.
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