A study published in the journal Cell demonstrates that dietary sugar increases the risk of metabolic syndrome by disrupting gut microbiota and suppressing protective T helper 17 (Th17) cells.
Consumption of a high-fat diet increases the risk of diabetes, obesity, cardiovascular disease, and metabolic syndrome. Although the causative link between a high-fat diet and metabolic risk is not completely known, it has been hypothesized that diet-induced intestinal inflammation can be a potential contributor.
The intestinal immune system is regarded as a vital regulator of metabolic homeostasis. CD4 T cells are major regulators of intestinal immune responses to dietary antigens. Studies have identified certain cell types that exhibit both promoting and protective effects in metabolic syndrome. These cell types are Th17 cells and type 3 innate lymphoid cells (ILC3).
The gut microbiota plays a crucial role in regulating intestinal immune responses, including Th17 cell and ILC3 responses. High-fat diet-induced changes in gut microbiota composition is known to promote metabolic syndrome by altering energy metabolism and immune responses.
In the current study, scientists have determined the relationship between microbiota-controlled intestinal immune responses and diet-induced obesity and metabolic syndrome.
Impact of a high-fat diet in metabolic syndrome
The comparison of immune responses induced by standard diet and high-fat diet in mice revealed that high-fat diet induces the symptoms of metabolic syndrome, including body weight gain, insulin resistance, and glucose intolerance.
Regarding intestinal immunity, high-fat diet was found to significantly reduce the expression and functionality of Th17 cells. The diet also reduced the secretion of interleukin 17 (IL-17), a cytokine produced by Th17 cells.
Mechanistically, high-fat diet caused a rapid loss of commensal microbiota responsible for inducing Th17 cells. This subsequently led to significant depletion of Th17 cells before the development of metabolic syndrome.
Further experiments revealed that commensal microbiota-induced Th17 cells play an essential role in ensuring microbiota-mediated protection against high-fat diet-related obesity and metabolic syndrome.
Impact of dietary sugar in metabolic syndrome
Three major harmful components of high-fat diet include excess fat, low dietary fiber, and high sugar content. Of these components, high level of sugar was identified as the main causal factor of diet-induced obesity and metabolic syndrome.
Mechanistically, dietary sugar promoted the growth of Faecalibaculum rodentium in an ILC3-dependent manner. The overgrowth of this Gram-positive bacterium displaced the commensal gut microbiota, leading to a depletion of intestinal commensal Th17 cells and subsequent diet-mediated induction of obesity and metabolic syndrome in mice.
However, the findings revealed that the elimination of dietary sugar is not sufficient to ensure protection. Restoration of Th17 expression and functionality by immune therapies is also required to protect the mice against diet-induced metabolic complications.
Th17 cell-mediated protection against metabolic syndrome
Absorption of dietary lipid by intestinal epithelial cells is a known regulator of metabolic syndrome. Th17 cell-secreting cytokine IL-17 is known to maintain intestinal barrier integrity by regulating epithelial cells.
The lipid content measurement in various tissues of mice fed with a high-fat diet revealed that in the presence of Th17 cells, intestinal epithelial cells absorb a lesser amount of dietary lipid. Mechanistically, Th-17 cell-secreted IL-17 suppressed the epithelial expression of fatty acid transporter CD36, leading to reduced lipid uptake and absorption across the intestinal epithelium.
The study provides an interactome of dietary components, gut microbiota, and intestinal immune cells that regulate the pathophysiology of high-fat diet-induced metabolic complications, such as obesity, type 2 diabetes, and metabolic syndrome.
The study identifies dietary sugar as the major deleterious component of a high-fat diet to increase the risk of metabolic disorders. Based on the findings, dietary modifications, together with immune interventions, are required to ensure full protection against diet-induced metabolic disorders.
As mentioned by the scientists, the study only focuses on the early stages of metabolic changes induced by a high-fat diet. Since diet-induced intestinal inflammation does not occur at early time points, future studies are required to decipher the long-term effects and protective mechanisms of Th17 cells in systemic disease.