Published: March 21, 2022
Authors: Sophia M. Hochrein, Hao Wu, Miriam Eckstein, Jan Van den Bossche, E. Dale Abel, Martin Vaeth
- Sugar causes significant inflammation
- Eating excess sugar and other carbohydrates, over time, could lead to the development of autoimmune diseases
- New, targeted treatments which don’t weaken the whole immune system could be developed in the future with these findings
The University of Wuerzburg wrote a great summary of this study on sugar and inflammation here.
Their key takeaways were that:
Sugar causes significant inflammation in the body and can be a factor in the development of autoimmune diseases.
Specifically that “People who consume sugar and other carbohydrates in excess over a long period of time have an increased risk of developing an autoimmune disease.”
“According to the researchers, these new findings pave the way for the development of targeted therapy of autoimmune diseases… without curtailing protective immune cell functions.”
Technical details from the study
“Autoimmune diseases, including multiple sclerosis (MS) and inflammatory bowel disease (IBD), are a heterogeneous group of pathologies with tissue-specific characteristics but common immunological hallmarks, such as T cell-mediated inflammation. T helper 17 (Th17) cells are implicated in the pathogenesis of most autoimmune diseases and targeting their effector cytokines showed promising clinical efficacy in psoriasis, IBD, and rheumatoid arthritis (RA).
The molecular mechanisms that promote the pathogenicity of Th17 cells remain incompletely understood but culminating evidence suggest that dietary factors contribute to the development and progression of autoimmune diseases.
Nutritional patterns that are characterized by high-calorie, high-salt, and excess sugar intake (collectively termed the “western diet”) are correlated with metabolic and inflammatory disorders and are considered as risk factors for autoimmunity.
How changes in systemic metabolism influence local inflammatory processes is complex, but recent data suggest that metabolic reprogramming of lymphocytes contributes significantly to the development of autoimmune diseases.”
“… we show that GLUT3 and ACLY directly control the epigenetic program of (pathogenic) Th17 cells through locus-specific histone acetylation. The interrelation between nutrient consumption and gene regulation by post-translational protein modifications, including the acetylation of histones, was first demonstrated in yeast and cancer cells.
More recently, and in line with our findings, a direct link between the glycolytic activity and the epigenetic remodeling of T cells has been established.
In cytotoxic T cells and Th1 cells, defective nutrient uptake in response to elevated extracellular potassium levels or T cell-specific deletion of lactate dehydrogenase A (LDHA), the rate-limiting enzyme for converting pyruvate to lactate, diminished cytosolic acetyl-CoA levels, and histone acetylation.
Ablation of LDHA also abolished the proliferation and effector differentiation of Th17 cells, which was—at least in part—due to altered epigenetic regulation of the Il17 locus.
However, LDHA deletion almost completely abolished aerobic glycolysis and the differentiation of all T cell subsets, whereas T cell-specific inactivation of GLUT3 affected primarily the effector functions of Th17 cells.
These data suggest that quantitative and/or qualitative thresholds exist that metabolically uncouple T cell activation from effector function, thus providing a therapeutic window to target specifically the pathogenic functions of Th17 cells.
In line with this notion, we here show that the natural compound 2-HC, an over-the-counter dietary supplement for weight loss therapy, ameliorates EAE in mice and abolishes inflammatory cytokine responses in murine and human Th17 cells.
These proof-of-concept experiments establish that GLUT3 and ACLY are promising metabolic checkpoints in lymphocytes that can be targeted to treat inflammatory diseases, in which Th17 cells play an important pathophysiological role.”