Erythrocyte saturated fatty acids and systemic inflammation in adults

Abstract

Objective The role of saturated fatty acids (SFAs) in chronic disease remains controversial; inflammation is one pathway by which SFAs influence the risk of chronic disease. We aim to investigate the associations between red blood cell (RBC) phospholipid SFAs and systemic inflammation. Methods As part of a randomized controlled trial, we measured RBC phospholipid FA composition among 55 generally healthy adults twice at three-month intervals. We estimated associations of RBC total SFAs and two major SFA subtypes, palmitic and stearic acids, with C-reactive protein (CRP), interleukin-6 (IL-6), white blood count (WBC), and a composite inflammation measure using generalized estimating equations in multivariable FA substitution models. Results Mean (±SD) SFA level across both visits was 45±3% of the total RBC FAs, mainly palmitic (21±1%) and stearic (17±3%) acids. In models adjusted for age, sex, race, smoking, BMI, statin use, aspirin use, transunsaturated FAs, and ω3FAs, SFAs were significantly associated with IL-6 (20% increase per 1 SD increment; 95% CI: 0.03%, 43%; P=0.05) and the composite inflammation measure (P=0.05) and marginally associated with CRP (34% increase; − 1%, 81%; P=0.06), but not associated with WBC. Stearic acid was positively associated with CRP (35% increase; 2%, 79%; P=0.04). Palmitic acid was marginally associated with the composite inflammation measure (P=0.06) and, upon additional ω6FA adjustment, significantly associated with IL-6 (15% increase; 0.4%, 27%; P=0.006). Conclusions RBC SFAs, which represent longer-term dietary intake, are positively associated with inflammation. In particular, palmitic acid was associated with IL-6, and stearic acid was associated with CRP after multivariable adjustment.

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non‐Hodgkin lymphoma

“…11 In addition, the even-numbered SFA and MUFA were found to be correlated with composite inflammation measures 12 and may thus influence risk of NHL via pro-inflammatory mechanisms. 12 However, oddnumbered SFA [e.g., pentadecanoic acid (15:0) and heptadecanoic acid (17:0)] primarily reflect dairy fat consumption and not endogenous synthesis. 13 A meta-analysis suggested a positive association of dairy product consumption with risk of NHL.…”

“…For example, in vivo study treatment with ST1326, an inhibitor of carnitine‐palmitoyl transferase 1A, prevented lymphomagenesis in mice by reducing the availability of a fundamental substrate for de novo lipogenesis . In addition, the even‐numbered SFA and MUFA were found to be correlated with composite inflammation measures and may thus influence risk of NHL via pro‐inflammatory mechanisms . However, odd‐numbered SFA [e.g., pentadecanoic acid (15:0) and heptadecanoic acid (17:0)] primarily reflect dairy fat consumption and not endogenous synthesis .…”

Factors Associated with Multiple Biomarkers of Systemic Inflammation

“…Higher intakes of saturated fat were positively associated with CRP, IL-6, and ICAM-1 (73). In another study, erythrocyte fatty acid composition in 55 healthy adults was compared to serum CRP and IL-6 concentrations (74). In multivariate models, total saturated fatty acids were modestly associated with IL-6 ( P =0.05) and CRP ( P =0.06), but palmitic and stearic acids, specifically, were significantly associated with IL-6 ( P =0.006) and CRP ( P =0.04), respectively (74).…”

“…In another study, erythrocyte fatty acid composition in 55 healthy adults was compared to serum CRP and IL-6 concentrations (74). In multivariate models, total saturated fatty acids were modestly associated with IL-6 ( P =0.05) and CRP ( P =0.06), but palmitic and stearic acids, specifically, were significantly associated with IL-6 ( P =0.006) and CRP ( P =0.04), respectively (74). Finally, a population-based dietary inflammatory index developed by Shivappa, et al,(51) which scored the inflammatory potential for a variety of dietary components based on extensive primary literature evaluating dietary associations with a panel of inflammation markers (CRP, IL-1β, IL-4, IL-6, IL-10, and TNF-α), found an overall positive association of saturated fat and inflammation.…”

Regulation of fatty acid synthesis in immune cells

“…In immune cells, fatty acids are used either as fuel for cellular metabolism through oxidation or as major components of membranes for cells or organelles such as the endoplasmic reticulum (ER) or Golgi body . Studies have also identified roles of fatty acids in the immune response and inflammation, that is saturated fatty acids promote inflammation, whereas polyunsaturated fatty acids exert anti‐inflammatory effects . Fatty acid metabolism, including FAS in immune cells, is illustrated in Figure .…”