Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.

The effects of colon-derived butyrate on intestinal cell proliferation are controversial. In vitro studies suggest an inhibitory effect, and in vivo studies suggest the opposite, but neither type of study has been based on a physiologically relevant, intracolonic supply of butyrate. In this study, piglets (n = 24) were fed sow's milk replacement formula and randomized into 4 equal groups: 1) control; 2) cecal butyrate infusion at a rate equal to that produced in the colon; 3) inulin supplementation at a concentration previously found to lower cecal cell proliferation; and 4) butyrate infusion plus inulin supplementation. After 6 d of oral feeding, cecal butyrate infusions were initiated for a period of 4 d. Cecal, distal colonic, jejunal, and ileal cell proliferation, apoptosis, and morphology were evaluated and serum concentration of glucagon-like peptide-2 (GLP-2) was measured. Butyrate or inulin did not affect GLP-2, weight gain, apoptosis, intestinal injury scores, cecal or colon crypt depth, and jejunal or ileal villus height. For cell proliferation, there was a significant interaction between inulin, butyrate, and tissue (P = 0.007). Inulin modified the effect of butyrate (butyrate × inulin interaction in cecum, P = 0.001; in distal colon, P = 0.018; in ileum, P = 0.001; and in jejunum, P = 0.003). In the absence of inulin, butyrate caused a 78– 119% increase in cell proliferation in the ileum, distal colon, jejunum, and cecum (P ≤ 0.002). Thus, at an entry rate into the colon within the physiological range, butyrate caused increased intestinal cell proliferation, but inulin tended to block this effect. Thus, intracolonic butyrate may enhance intestinal growth during infancy.

Background: Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascula

In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short‐term increases in dietary PA or OA would result in corresponding changes in the FA composition of skeletal muscle diacylglycerol (DAG) and triacylglycerol (TAG) and/or the specific FA selected for β‐oxidation. Healthy males (N = 12) and females (N = 12) ingested a low‐PA diet for 7 days. After fasting measurements of the serum acylcarnitine (AC) profile, subjects were randomized to either high‐PA (HI PA) or low‐PA/high‐OA (HI OA) diets. After 7 days, the fasting AC measurement was repeated and a muscle/fat biopsy obtained. FA composition of intramyocellular DAG and TAG and serum AC was measured. HI PA increased, whereas HI OA decreased, serum concentration of 16:0 AC (P < 0.001). HI OA increased 18:1 AC (P = 0.005). HI PA was associated with a higher PA/OA ratio in muscle DAG and TAG (DAG: 1.03 ± 0.24 vs. 0.46 ± 0.08, P = 0.04; TAG: 0.63 ± 0.07 vs. 0.41 ± 0.03, P = 0.01). The PA concentration in the adipose tissue DAG (µg/mg adipose tissue) was 0.17 ± 0.02 in those receiving the HI PA diet (n = 6), compared to 0.11 ± 0.02 in the HI oa group (n = 4) (P = 0.067). The relative PA concentration in muscle DAG and TAG and the serum palmitoylcarnitine concentration was higher in those fed the high‐PA diet.

Background: Oleic acid (OA) is oxidized more rapidly than is palmitic acid (PA). Objective: We hypothesized that changing the dietary intakes of PA and OA would affect fatty acid oxidation and energy expenditure. Design: A double-masked trial was conducted in 43 healthy young adults, who, after a 28-d, baseline, solid-food diet (41% of energy as fat, 8.4% as PA, and 13.1% as OA), were randomly assigned to one of two 28-d formula diets: high PA (40% of energy as fat, 16.8% as PA, and 16.4% as OA; n = 21) or high OA (40% of energy as fat, 1.7% as PA, and 31.4% as OA; n = 22). Differences in the change from baseline were evaluated by analysis of covariance. Results: In the fed state, the respiratory quotient was lower (P = 0.01) with the high OA (0.86 ± 0.01) than with the high-PA (0.89 ± 0.01) diet, and the rate of fat oxidation was higher (P = 0.03) with the high-OA (0.0008 ± 0.0001) than with the high-PA (0.0005 ± 0.0001 mg · kg fat-free mass⁻¹ · min⁻¹) diet. Resting energy expenditure in the fed and fasting states was not significantly different between groups. Change in daily energy expenditure in the high-OA group (9 ± 60 kcal/d) was significantly different from that in the high-PA group (−214 ± 69 kcal/d; P = 0.02 or 0.04 when expressed per fat-free mass). Conclusions: Increases in dietary PA decrease fat oxidation and daily energy expenditure, whereas decreases in PA and increases in OA had the opposite effect. Increases in dietary PA may increase the risk of obesity and insulin resistance.

Background: The Western diet increases risk of metabolic disease.Objective: We determined whether lowering the ratio of saturated fatty acids to monou