From:  Nutrient-driven immunometabolism in metabolic disease

 Immunometabolism dysregulation in key metabolic diseases.

Disease/TissueKey immune playersDriving dietary/Dysbiotic factorsDysregulated metabolic pathwaysPathogenic outcome
Obesity (adipose tissue)ATMs, CD8+ T cells,
↓ Tregs [153]
Excess SFA, fructose [123]Glycolysis in ATMs; impaired FAO in TregsInsulin resistance, chronic systemic inflammation [157].
T2D (pancreatic islets)Islet-associated macrophages, T cells [159]Hyperglycemia, AGEs [85]↑ Glycolysis & IL-1β production in macrophagesβ-cell dysfunction & apoptosis; failure of insulin secretion [160].
NAFLD/NASH (liver)Kupffer cells, monocyte-derived macrophages [161]SFA, fructose, gut-derived endotoxins [162]Glycolytic shift, impaired OXPHOS in KCs [163]
Hepatocyte injury, steatosis, inflammation, fibrosis [164].
Atherosclerosis (vascular wall)Intimal macrophages (foam cells), T cells [165]High SFA, cholesterol, trans-fats [171]Impaired cholesterol efflux, glycolytic shift in foam cells [172]Plaque formation, progression, and instability [173].

AGEs: advanced glycation end products; ATMs: adipose tissue macrophages; FAO: fatty acid oxidation; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; OXPHOS: oxidative phosphorylation; SFA: saturated fatty acid; T2D: type 2 diabetes; Treg: regulatory T cell.