Nobiletin Prevents High-Fat Diet-Induced Dysregulation of Intestinal Lipid Metabolism and Attenuates Postprandial Lipemia

Objective: Nobiletin is a dietary flavonoid that improves insulin resistance and atherosclerosis in mice with metabolic dysfunction. Dysregulation of intestinal lipoprotein metabolism contributes to atherogenesis. The objective of the study was to determine if nobiletin targets the intestine to improve metabolic dysregulation in both male and female mice. Approach and Results: Triglyceride-rich lipoprotein (TRL) secretion, intracellular triglyceride kinetics, and intestinal morphology were determined in male and female LDL (low-density lipoprotein) receptor knockout, and male wild-type mice fed a standard laboratory diet or high-fat, high-cholesterol diet ± nobiletin using an olive oil gavage, radiotracers, and electron microscopy. Nobiletin attenuated postprandial TRL levels in plasma and enhanced TRL clearance. Nobiletin reduced fasting jejunal triglyceride accumulation through accelerated TRL secretion and lower jejunal fatty acid synthesis with no impact on fatty acid oxidation. Fasting-refeeding experiments revealed that nobiletin led to higher levels of phosphorylated AKT and FoxO1 (forkhead box O1) and normal Srebf1-c expression indicating increased insulin sensitivity. Intestinal length and weight were diminished by high-fat feeding and restored by nobiletin. Both fasting and postprandial plasma GLP-1 (glucagon-like peptide-1; and likely GLP-2) were elevated in response to nobiletin. Treatment with a GLP-2 receptor antagonist, GLP-2(3-33), reduced villus length in high fat-fed mice but did not impact TRL secretion in any diet group. In contrast to males, nobiletin did not improve postprandial lipid parameters in female mice. Conclusions: Nobiletin opposed the effects of the high-fat diet by normalizing intestinal de novo lipogenesis through improved insulin sensitivity. Nobiletin prevents postprandial lipemia because the enhanced TRL clearance more than compensates for increased TRL secretion.

Trends in Food Innovation: An Interventional Study on the Benefits of Consuming Novel Functional Cookies Enriched with Olive Paste

Olive paste may exert bioactivity due to its richness in bioactive components, such as oleic acid and polyphenols. The present interventional human study investigated if the fortification of cookies with olive paste and herbs may affect postprandial lipemia, oxidative stress, and other biomarkers in healthy volunteers. In a cross-over design, 10 healthy volunteers aged 20–30 years, consumed a meal, rich in fat and carbohydrates (50 g cookies). After a washout week, the same volunteers consumed the same cookie meal, enhanced with 20% olive paste. Blood sampling was performed before, 0.5 h, 1.5 h, and 3 h after eating. Total plasma antioxidant capacity according to FRAP, ABTS, and resistance to copper-induced plasma oxidation, serum lipids, glucose, uric acid, and antithrombotic activity in platelet-rich plasma were determined at each timepoint. There was a significant decrease in triglycerides’ concentration in the last 1.5 h in the intervention compared to the control group (p < 0.05). A tendency for a decrease in glucose levels and an increase in the plasma antioxidant capacity was observed 0.5 h and 1.5 h, respectively, in the intervention compared to the control group. The remaining biomarkers did not show statistically significant differences (p > 0.05). More clinical and epidemiological studies in a larger sample are necessary in order to draw safer conclusions regarding the effect of olive paste on metabolic biomarkers, with the aim to enhance the industrial production of innovative functional cookies with possible bioactivity.

Clitoria ternatea Flower Extract Attenuates Postprandial Lipemia and Increases Plasma Antioxidant Status Responses to a High-Fat Meal Challenge in Overweight and Obese Participants

High-fat (HF) meal-induced postprandial lipemia, oxidative stress and low-grade inflammation is exacerbated in overweight and obese individuals. This postprandial dysmetabolism contributes to an increased risk of cardiovascular disease and metabolic disorders. Clitoria ternatea flower extract (CTE) possesses antioxidant potential and carbohydrate and fat digestive enzyme inhibitory activity in vitro. However, no evidence supporting a favorable role of CTE in the modulation of postprandial lipemia, antioxidant status and inflammation in humans presently exists. In the present study, we determine the effect of CTE on changes in postprandial glycemic and lipemic response, antioxidant status and pro-inflammatory markers in overweight and obese men after consumption of an HF meal. Following a randomized design, sixteen participants (age, 23.5 ± 0.6 years, and BMI, 25.7 ± 0.7 kg/m2) were assigned to three groups that consumed the HF meal, or HF meal supplemented by 1 g and 2 g of CTE. Blood samples were collected at fasting state and then at 30, 60, 90, 120, 180, 240, 300 and 360 min after the meal consumption. No significant differences were observed in the incremental area under the curve (iAUC) for postprandial glucose among the three groups. Furthermore, 2 g of CTE decreased the iAUC for serum triglyceride and attenuated postprandial serum free fatty acids at 360 min after consuming the HF meal. In addition, 2 g of CTE significantly improved the iAUC for plasma antioxidant status, as characterized by increased postprandial plasma FRAP and thiol levels. Postprandial plasma glutathione peroxidase activity was significantly higher at 180 min after the consumption of HF meal with 2 g of CTE. No significant differences in the level of pro-inflammatory cytokines (interleukin-6, interleukin-1β and tumor necrosis factor-α) were observed at 360 min among the three groups. These findings suggest that CTE can be used as a natural ingredient for reducing postprandial lipemia and improving the antioxidant status in overweight and obese men after consuming HF meals.

The acute effect of incorporating lettuce or watercress into a moderately high-fat meal on postprandial lipid, glycemic response, and plasma inflammatory cytokines in healthy young men: a randomized crossover trial

Background Postprandial responses to food mostly depend on the composition of the meal and the consumption of vegetables may modulate this postprandial state. In this study, the effects of lettuce or watercress consumption with a moderately high-fat meal (40% kcal from fat) on postprandial lipemia, glycemia, and inflammatory cytokines were determined in healthy men. Methods This randomized, 3-arm, crossover study was conducted in sixteen healthy young men with a mean ± SEM age and body mass index (in kg/m2) of 22.8 ± 0.5 years old and 23.7 ± 1.16, respectively. Lettuce and watercress were added to the test meal in portions of 100 g and cellulose was added to the control meal. Thereafter, blood samples were collected by passing 0, 1, 2, 3, and 4 h for analysis. The postprandial response was measured in plasma glucose, triglycerides (TG), total cholesterol, high-density-lipoproteins cholesterol (HDL-C), and low-density-lipoproteins cholesterol (LDL-C), as the area under the postprandial curve (AUC). Moreover, plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined once before and once 4 h after the meal’s consumption. Results The 0–4-h AUCs for glucose (385.7, 361.9, and 382.3 mg/dL for the control, lettuce, and watercress meals, respectively) were calculated to be lower when meal was consumed with lettuce compared to the control (P < 0.05) and watercress (P < 0.01) meals. The maximum values of insulin were obtained as 43.8 ± 18.8, 33.5 ± 19.5, and 42.8 ± 17.7 μIU/mL for the control, lettuce, and watercress meals, respectively. As well, the lettuce-containing meal more reduced the AUC for insulin compared with the control (P < 0.05), but not watercress. Notably, plasma TG, total cholesterol, HDL-C, and LDL-C had no significant differences among the meals. Moreover, the levels of plasma IL-6 and TNF-α did not differ among the meals. Conclusion In this study on healthy men, the addition of lettuce to a moderately high-fat meal delayed the postprandial glycemic response. However, the effect of the consumption of these vegetables on postprandial responses in subjects with cardiometabolic risk factors remains to be elucidated yet. This clinical trial was registered at the Iran Clinical Trials Registration Office (IRCT) on March 3, 2018, with an ID of IRCT20160702028742N4 (https://www.irct.ir/user/trial/23233/view).

Alternative Foods in Cardio-Healthy Dietary Models That Improve Postprandial Lipemia and Insulinemia in Obese People

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.

Circulating MicroRNA Responses to Postprandial Lipemia with or without Prior Exercise

Repeated exposure to a high-fat meal triggers inflammation and oxidative stress, contributing to the onset of cardiometabolic diseases. Regular exercise prevents cardiometabolic diseases and a prior bout of acute endurance exercise can counteract the detrimental cardiovascular effects of a subsequent high-fat meal. Circulating microRNAs (ci-miRs) are potential mediators of these vascular effects through regulation of gene expression at the posttranscriptional level. Therefore, we investigated the expression of ci-miRs related to vascular function (miR-21, miR-92a, miR-126, miR-146a, miR-150, miR-155, miR-181b, miR-221, miR-222) in plasma from healthy, recreationally to highly active, Caucasian adult men after a high-fat meal with (EX) and without (CON) a preceding bout of cycling exercise. Ci-miR-155 was the only ci-miR for which there was a significant interaction effect of high-fat meal and exercise (p=0.050). Ci-miR-155 significantly increased in the CON group at two (p=0.007) and four hours (p=0.010) after the high-fat meal test, whereas it significantly increased in the EX group only four hours after the meal (p=0.0004). There were significant main effects of the high-fat meal on ci-miR-21 (p=0.01), ci-miR-126 (p=0.02), ci-miR-146a (p=0.02), ci-miR-181b (p=0.02), and ci-miR-221 (p=0.008). Collectively, our results suggest that prior exercise does not prevent high-fat meal-induced increases in vascular-related ci-miRs.

Determinants of Postprandial Triglycerides Across the Spectrum of Aging

Objectives Elevated postprandial triglycerides (TG) are a risk factor for cardiovascular disease, and older adults exhibit greater postprandial lipemia (PPL) compared to younger adults. However, determinants of PPL, especially in older populations, remain poorly defined. This cross-sectional study examined the influence of body composition, lifestyle behaviors, and metabolic risk factors for PPL across the aging spectrum. Methods We recruited individuals evenly distributed between the ages of 50–89 years (50% male; 50% female). Participants completed diet and physical activity questionnaires and wore an accelerometer for 5 days. Body composition was measured via bioelectrical impedance. Following an overnight fast, participants also completed an abbreviated fat tolerance test: a blood draw was performed before and 4 hours after consumption of a high-fat meal (9 kcal/kg; 73% fat) to determine fasting and peak postprandial metabolic responses. Results 56 participants (age groups: 50s, n = 15; 60s, n = 15; 70s, n = 15; 80s, n = 11) completed the study. Fasting TG did not differ across age groups (50s: 99.7 ± 50.1 mg/dL; 60s: 114.3 ± 71.1 mg/dL; 70s: 102.9 ± 45.0 mg/dL; 80s: 86.9 ± 39.5 mg/dL; P = 0.63). There was also no difference in 4-hour TG across age groups (50s: 162.9 ± 76.9 mg/dL; 60s: 181.9 ± 99.9 mg/dL; 70s: 130.8 ± 82.0 mg/dL; 80s: 130.8 ± 60.6 mg/dL; P = 0.40). Across age groups, variables significantly correlated (p's &lt; 0.05) with 4-hour TG included BMI (r = 0.29), visceral adiposity (r = 0.31), ALT (r = 0.37), fasting glucose (r = 0.27), 4-hour glucose (r = 0.34) and alcohol intake (r = 0.33). In a backward elimination regression (R2 = 0.31), the most predictive variables of 4-hour TG were 4-hour glucose (β = 0.31; P = 0.01), ALT (β = 0.33; P = 0.007), and alcohol intake (β = 0.25; P = 0.04). Conclusions In older adults aged 50–89, we identified ALT, postprandial glucose, and alcohol intake as key determinants of postprandial TG. Future studies should aim to explore the relationship between liver health, insulin resistance, alcohol intake, and PPL across the aging spectrum. Funding Sources Donna Cadwalader Research and Development Grant, College of Education and Human Sciences and Oklahoma State University Foundation.

Emulsion Colloidal Gastric Stability and Lipid Droplet Physical State Modulate Gastric Emptying and Short-Term Satiety in Healthy Men

Objectives The aim of this randomized crossover study was to investigate the influences of TAG droplet physical state at 37°C and emulsion gastric colloidal stability on gastric emptying (GE), postprandial lipemia and satiety in healthy men. It was hypothesized that emulsions susceptible to flocculation in the stomach would augment GE compared to acid stable emulsions, and that the acute lipemic and satiety responses would be attenuated for emulsions containing crystalline TAG and/or an acid unstable emulsifier. Methods Twenty % palm stearin or palm olein emulsions with similar particle size distributions where formulated using either Tween80 (acid stable emulsifier) or Span60 (acid unstable emulsifier). The four emulsions contained partially crystalline droplets that remained stable (SS) or destabilized (SU) or contained liquid droplets that remained stable (LS) or destabilized (LU) when exposed to simulated in vitro gastric conditions. Fifteen healthy adult male non-restrained eaters (mean ± SD age: 24.9 ± 4.5; BMI: 26.0 ± 2.0 kg/m2; fasting TAG: 0.9 ± 0.3 mmol/L) consumed 250 mL of one of the emulsions on four occasions separated by at least 6 days. Baseline fasting and 6-hr postprandial ultrasound gastric antrum measurements, satiety visual analogue scales (VAS), and blood samples for analysis of plasma TAG and hunger and satiety hormones were collected. Results Gastric antrum area decreased faster (P ≤ 0.01) for the acid unstable emulsions (SU and LU) indicating faster GE. Postprandial TAG response did not differ significantly between any of the emulsions, but there were differences in postprandial satiety responses. 3-hr incremental area under the curve (iAUC) was significantly lower for hunger (P = 0.021) and desire to eat (P = 0.031) ratings and 6-hr iAUC was significantly higher for ghrelin (P = 0.028) with LS compared to SU. Plasma PYY and GLP-1 change from baseline values were also higher following consumption of LS compared to LU (P = 0.028) (for PYY), and compared to SU (P = 0.008) and LU (P = 0.001) (for GLP-1). Conclusions Emulsion phase separation in the stomach was associated with delayed GE, which corresponded to enhanced satiety with the acid stable emulsion containing TAG in the liquid state. Funding Sources Canada's Natural Sciences and Engineering Research Council.