Revisiting the Immunometabolic Basis for the Metabolic Syndrome from an Immunonutritional View

Abstract

Metabolic syndrome (MetS) implies different conditions where insulin resistance constitutes a major hallmark of the disease. The disease incurs a high risk for the development of cardiovascular complications, and takes its toll in regard to the gut-liver axis (pancreas, primary liver and colorectal)-associated immunity. The modulation of immunometabolic responses by immunonutritional factors (IFs) has emerged as a key determinant of the gut-liver axis' metabolic and immune health. IFs from plant seeds have shown in vitro and pre-clinical effectiveness primarily in dealing with various immunometabolic and inflammatory diseases. Only recently have immunonutritional studies established the engagement of innate intestinal immunity to effectively control immune alterations in inflamed livers preceding the major features of the MetS. However, integrative analyses and the demonstration of causality between IFs and specific gut-liver axis-associated immunometabolic imbalances for the MetS remain ill-defined in the field. Herein, a better understanding of the IFs with a significant role in the MetS, as well as within the dynamic interplay in the functional differentiation of innate immune key effectors (i.e., monocytes/macrophages), worsening or improving the disease, could be of crucial relevance. The development of an adequate intermediary phenotype of these cells can significantly contribute to maintaining the function of T_regs and innate lymphoid cells for the prevention and treatment of MetS and associated comorbidities.

Keywords: immunonutrition; insulin resistance; macrophage; metabolic syndrome; obesity; type 2 diabetes.

Figure 1

Schematic diagram for the interaction of the genetic and environmental factors influencing the control of hepatic fat accumulation by macrophages. ILCs, innate lymphoid cells; FA, fatty acids.

Figure 2

Schematic hypothesis to explain the potential different contribution of TLR4 to the inflammatory phenotype of macrophages in the metabolic syndrome. SETIs, serine-type protease inhibitors; LPS, bacterial lipopolysaccharide; IRF3, interferon regulatory factor 3; IFNs, interferons; IS, insulin sensitivity. Small-dotted line represents the sequence of events triggered by the activation of TLR4 by the prototypical agonist LPS (red symbols and arrows). Solid line represents the sequence of events triggered by the activation of TLR4 by SETIs (green symbols and arrows). Large-dotted line represents the influence of insulin on the NRLP3 expression.