From:  Nutrient-driven immunometabolism in metabolic disease

 Immunometabolism impact of dietary components and patterns.

Dietary component/PatternKey immune/Cellular targetsImmunometabolism effectResulting immune phenotype/Outcome
High glycemic carbs/FructosemTOR, HIF-1α, NLRP3 [80]↑ Glycolysis,
↑ Oxidative Stress
Pro-inflammatory M1/Th1/Th17; β-cell dysfunction [85].
Saturated fats (e.g., palmitate)TLR4, NLRP3, ceramide synthesis [86, 87]↑ Inflammatory signaling,
↓ OXPHOS
Pro-inflammatory ATMs, hepatic inflammation, and insulin resistance [88].
Omega-3 PUFAs (EPA/DHA)GPR120, PPARγ, NLRP3 [89, 90]↑ SPMs,
↓ NLRP3 activation,
↑ FAO
Anti-inflammatory M2/Treg polarization; resolved inflammation [91].
Vitamin DVDR [92]↑ Antimicrobial peptides,
↑ Treg differentiation
Enhanced barrier defense, tolerogenic immune environment [93].
ZincZIP/ZnT transporters, NF-κB [94]Antioxidant, inhibits NLRP3Proper lymphocyte development, controlled inflammation [95].
Polyphenols (e.g., resveratrol)AMPK, SIRT1, Nrf2, NF-κB [96]↑ OXPHOS/Mitophagy, ↑ Antioxidant defensesReduced oxidative stress, anti-inflammatory, enhanced resilience [97].
Western dietGut microbiota, TLR4, mTOR [98]Dysbiosis,
↑ Endotoxemia,
↑ Glycolysis
Systemic metaflammation: basis for metabolic diseases [99].
Mediterranean dietGut microbiota, AMPK, PPARγ [100]↑ SCFA production, favorable n-6:n-3 ratioReduced CRP/IL-6, improved cardiometabolic health [101].
Ketogenic diet/Intermittent fastingAMPK, SIRTs, HDACs (via BHB) [102]↑ Ketolysis,
↑ Autophagy,
↑ OXPHOS
Reduced NLRP3 activity, enhanced memory T cell function.

AMPK: AMP-activated protein kinase; ATMs: adipose tissue macrophages; CRP: C-reactive protein; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FAO: fatty acid oxidation; GPR: G protein-coupled receptor; HDACs: histone deacetylases; HIF: hypoxia-inducible factor; mTOR: mechanistic target of rapamycin; NF-κB: nuclear factor κB; NLRP3: NOD-like receptor family pyrin domain containing 3; Nrf2: nuclear factor erythroid 2-related factor 2; OXPHOS: oxidative phosphorylation; PPARγ: peroxisome proliferator-activated receptor gamma; PUFAs: polyunsaturated fatty acids; SCFAs: short-chain fatty acids; SIRT: sirtuin; SPMs: specialized pro-resolving mediators; TLR4: toll-like receptor 4; Treg: regulatory T cell; VDR: vitamin D receptor; ZIP/ZnT: zinc importer/zinc transporter proteins.