Postprandial lipopolysaccharide after a saturated compared to monounsaturated fatty acid enriched high fat meal in older adults: a randomized control trial

Lipopolysaccharide (LPS), derived from gram-negative bacteria, is associated with inflammation. Serum LPS concentrations modestly rise after high-fat meals, known as metabolic endotoxemia, with saturated fatty acids (SFA) potentially producing a greater response than other fatty acids. This study examined whether SFA, compared with monounsaturated fatty acids (MUFA), differentially affects postprandial LPS and inflammatory responses in older adults with overweight or obesity. In a randomized crossover study, older adults were educated to consume 3-days of a low-fat diet prior to each high-fat (46%) meal (~ 550 kcal) enriched with either MUFA (20 g; 57% total fat) or SFA (15 g; 42% total fat), both matched for energy and macronutrients. Meals included foods enriched in MUFA (peanuts) or SFA (butter) to achieve these differences and were given in random order on two separate study days. Blood samples were collected before and 30, 120, 180, 240, 300, and 360 min after the meal to assess serum LPS, lipopolysaccharide binding protein (LBP), triglycerides, glucose, and inflammatory markers. Data were analyzed using repeated-measures ANOVA and a priori time points were compared between diets. Pearson correlations were used to determine associations between the change in postprandial LPS and inflammatory markers. Participants ( n = 16, 75% female) were 62.7 ± 4.8 years of age with a body mass index 33.4 ± 6.3 kg/m 2 . The postprandial rise of serum LPS at 4 h was twice as high after the SFA than MUFA meal ( p < 0.05) and LBP was also higher ( p < 0.05). There were no between-meal differences in other inflammatory markers. However, the increase in peak postprandial LPS was positively correlated with peak tumor necrosis factor-α after the SFA meal only ( p < 0.05). Consumption of SFA-enriched compared to MUFA-enriched meals led to a greater rise in postprandial serum LPS and LBP concentration. Overall, these findings suggest that a meal containing moderate energy and moderately elevated fat intake results in metabolic endotoxemia that is greater with a SFA-enriched meal and neither diet acutely upregulated postprandial inflammatory markers. ClinicalTrials.gov (NCT06348771). Registered 22 March, 2024.