Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play a direct role in regulating immune cell activation, differentiation and expansion, and inflammatory phenotypes. Understanding the complexities of lipid–immune interactions may have important implications for human health, as certain lipids or immune pathways may be beneficial in circumstances of acute infection yet detrimental in chronic inflammatory diseases. Further, there are key differences in the lipid effects between specific immune cell types and location (e.g., gut mucosal vs. systemic immune cells), suggesting that the immunomodulatory properties of lipids may be tissue-compartment-specific, although the direct effect of dietary lipids on the mucosal immune system warrants further investigation. Importantly, there is recent evidence to suggest that lipid–immune interactions are dependent on sex, metabolic status, and the gut microbiome in preclinical models. While the lipid–immune relationship has not been adequately established in/translated to humans, research is warranted to evaluate the differences in lipid–immune interactions across individuals and whether the optimization of lipid–immune interactions requires precision nutrition approaches to mitigate or manage disease. In this review, we discuss the mechanisms by which lipids regulate immune responses and the influence of dietary lipids on these processes, highlighting compelling areas for future research.

Western-style diets have been linked with dyslipidemia and inflammation, two well-known risk factors associated with cardiovascular disease (CVD). Dietary sphingomyelin (SM) has been reported to modulate gut microbiota, and lower serum lipids and inflammation in mice on Western-style diets. However, few studies have examined if nutritionally-relevant intake of dietary SM can impact atherosclerosis progression. Thus, the aim of this study was to determine if incorporating 0.1% (w/w) egg SM (ESM) (equivalent to ~750 mg/day in humans) into a high-fat (45% kcal), cholesterol-enriched diet (HFD) could prevent atheroprogression in apoE^−/− mice (n = 15/group). We found that mice fed with the ESM-rich diet had significantly lower epididymal fat mass (−46%) and tended to have higher spleen weights (+15%). There were no significant differences in serum lipids between groups. However, ESM-fed mice had significantly lower alanine aminotransferase (ALT) activity. Additionally, ESM-fed mice displayed significantly less aortic root lipid accumulation (−31%) compared to controls. This improvement in atherosclerosis was paired with over a two-fold reduction in circulating serum amyloid A (SAA) in ESM-fed mice. Finally, there was also a modulation of the gut microbiota with ESM supplementation. ESM may have the potential to prevent atherosclerosis, however further research in the clinical setting is warranted.

Background: High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. Methods: Twenty adults (age: 32–70 years; body mass index: 25.3–45.4 kg/m ² ) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. Results: After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo ( P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. Conclusions: Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.

We recently reported that the inclusion of whole eggs in plant-based diets (PBD) increased plasma choline, lutein, and zeaxanthin in individuals with metabolic syndrome (MetS). The objective of the current study was to evaluate whether this dietary pattern would protect against oxidative stress and low-grade inflammation, two common characteristics of MetS. We recruited 24 men and women with MetS, who, after following a PBD for 2 weeks (baseline), were randomly allocated to consume either two whole eggs with 70 g of spinach/day (EGG) or the equivalent amount of egg substitute with spinach (SUB) as breakfast for 4 weeks. After a 3-week washout, they were allocated to the alternate breakfast. We measured biomarkers of oxidation and inflammation at baseline and at the end of each intervention. Tumor necrosis factor-alpha, interleukin-6, monocyte protein attractant-1, liver enzymes, and C-reactive protein, as well as total antioxidant capacity, paraoxonase-1 (PON-1) activity, and other biomarkers of oxidation were not different at the end of EGG or SUB or when compared to baseline. However, plasma malondialdehyde (MDA) concentrations were lower (p < 0.05) during the EGG and baseline compared to SUB. In addition, the increases in dietary lutein and zeaxanthin previously observed had a strong positive correlation with PON-1 activity (r = 0.522, p < 0.01) only during the EGG period, whereas plasma zeaxanthin was negatively correlated with MDA (r = −0.437, p < 0.01). The number of participants with MetS was reduced from 24 during screening to 21, 13, and 17 during the BL, EGG, and SUB periods, respectively, indicating that eggs were more effective in reversing the characteristics of MetS. These data suggest that adding eggs to a PBD does not detrimentally affect inflammation or oxidative stress; on the contrary, eggs seem to provide additional protection against the biomarkers that define MetS.