Short-term high-calorie high-fat feeding induces hyperinsulinemia and blunts skeletal muscle microvascular blood flow in healthy humans.

Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P = 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow.

Cross-sectional associations of dietary patterns characterized by fat type with markers of cardiometabolic health.

BACKGROUND AND AIMS: Individual dietary fats can differentially impact on cardiometabolic health. However, their impact within a dietary pattern is not well understood, and warrants comparison with diet quality scores with a dietary fat focus. The aim of this study was to investigate cross-sectional associations between a posteriori dietary patterns characterized by fat type and cardiometabolic health markers, and compare these with two diet quality scores. METHODS AND RESULTS: UK Biobank adults with ≥two 24-h dietary assessments and data on cardiometabolic health were included (n = 24 553; mean age: 55.9 y). A posteriori dietary patterns (DP1; DP2) were generated through reduced rank regression (response variables: SFA, MUFA, PUFA). Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were created. Multiple linear regression analyses were used to investigate associations between standardized dietary patterns and cardiometabolic health (total cholesterol, HDL-C, LDL-C and VLDL-C cholesterol, triglycerides, C-reactive protein [CRP], glycated hemoglobin [HbA1c]). DP1, positively correlated with SFAs, MUFAs and PUFAs, characterized by higher nuts, seeds and vegetables intake and lower fruits and low-fat yoghurt intake, was associated with lower HDL-C (ß: -0.07; 95% CI: -0.10, -0.03) and triglycerides (-0.17; -0.23, -0.10) and higher LDL-C (0.07; 0.01,0.12), CRP (0.01; 0.01, 0.03) and HbA1c (0.16; 0.11,0.21). DP2, positively correlated with SFAs, negatively correlated with PUFAs, characterized by higher butter and high-fat cheese intake and lower nuts, seeds and vegetable intake, was associated with higher total cholesterol (0.10; 0.01, 0.21), VLDL-C (0.05; 0.02, 0.07), triglycerides (0.07; 0.01, 0.13), CRP (0.03; 0.02, 0,04) and HbA1c (0.06; 0.01, 0.11). Higher adherence to MDS and DASH was associated with favorable cardiometabolic health markers concentration. CONCLUSIONS: Irrespective of the method used, dietary patterns that encourage healthy fat consumption were associated with favorable cardiometabolic health biomarkers. This study strengthens the evidence for incorporation of dietary fat type into policy and practice guidelines for CVD prevention.

Impaired postprandial adipose tissue microvascular blood flow responses to a mixed-nutrient meal in first-degree relatives of adults with type 2 diabetes.

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FH+ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D.NEW & NOTEWORTHY Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.

Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high-glucose mixed meal in healthy young men.

KEY POINTS: Exercise, insulin-infusion and low-glucose mixed-nutrient meal ingestion increases muscle microvascular blood flow which in part facilitates glucose delivery and disposal. In contrast, high-glucose ingestion impairs muscle microvascular blood flow which may contribute to impaired postprandial metabolism. We investigated the effects of prior cycling exercise on postprandial muscle microvascular blood flow responses to a high-glucose mixed-nutrient meal ingested 3 and 24 h post-exercise. Prior exercise enhanced muscle microvascular blood flow and mitigated microvascular impairments induced by a high-glucose mixed meal ingested 3 h post-exercise, and to a lesser extent 24 h post-exercise. High-glucose ingestion 3 h post-exercise leads to greater postprandial blood glucose, non-esterified fatty acids, and fat oxidation, and a delay in the insulin response to the meal compared to control. Effects of acute exercise on muscle microvascular blood flow persist well after the cessation of exercise which may be beneficial for conditions characterized by microvascular and glycaemic dysfunction. ABSTRACT: Exercise, insulin-infusion and low-glucose mixed-nutrient meal ingestion lead to increased muscle microvascular blood flow (MBF), whereas high-glucose ingestion impairs MBF. We investigated whether prior cycling exercise could enhance postprandial muscle MBF and prevent MBF impairments induced by high-glucose mixed-nutrient meal ingestion. In a randomized cross-over design, eight healthy young men ingested a high-glucose mixed-nutrient meal (1.1 g glucose/kg body weight; 45% carbohydrate, 20% protein and 35% fat) after an overnight fast (no-exercise control) and 3 h and 24 h after moderate-intensity cycling exercise (1 h at 70-75% V̇O2peak ). Skeletal muscle MBF, measured directly by contrast-enhanced ultrasound, was lower at 60 min and 120 min postprandially compared to baseline in all conditions (P < 0.05), with a greater decrease occurring from 60 min to 120 min in the control (no-exercise) condition only (P < 0.001). Despite this meal-induced decrease, MBF was still markedly higher compared to control in the 3 h post-exercise condition at 0 min (pre-meal; 74%, P = 0.004), 60 min (112%, P = 0.002) and 120 min (223%, P < 0.001), and in the 24 h post-exercise condition at 120 min postprandially (132%, P < 0.001). We also report that in the 3 h post-exercise condition postprandial blood glucose, non-esterified fatty acids (NEFAs), and fat oxidation were substantially elevated, and the insulin response to the meal delayed compared to control. This probably reflects a combination of increased post-exercise exogenous glucose appearance, substrate competition, and NEFA-induced insulin resistance. We conclude that prior cycling exercise elicits long-lasting effects on muscle MBF and partially mitigates MBF impairments induced by high-glucose mixed-nutrient meal ingestion.

Dietary Patterns Characterized by Fat Type in Association with Obesity and Type 2 Diabetes: A Longitudinal Study of UK Biobank Participants.

BACKGROUND: The fat type consumed is considered a risk factor for developing obesity and type 2 diabetes (T2D). However, these associations have not been investigated using a dietary patterns approach, which can capture combinations of foods and fat type consumed. OBJECTIVES: This study aimed to investigate associations between dietary patterns with varying proportions of SFAs, MUFAs, or PUFAs and obesity, abdominal obesity, and self-reported T2D incidence. METHODS: This study included UK Biobank participants with 2 or more 24-h dietary assessments, free from the outcome of interest at recruitment, and with outcome data at follow-up (n = 16,523; mean follow-up: 6.3 y). Reduced rank regression was used to derive dietary patterns with SFAs, MUFAs, and PUFAs (% of energy intake) as response variables. Logistic regression, adjusted for sociodemographic and health characteristics, was used to investigate the associations between dietary patterns and obesity [BMI (kg/m2) ≥30], abdominal obesity (waist circumference; men: ≥102 cm; women: ≥88 cm) and T2D incidence. RESULTS: Two dietary patterns, DP1 and DP2, were identified: DP1 positively correlated with SFAs (r = 0.48), MUFAs (r = 0.67), and PUFAs (r = 0.56), characterized by higher intake of nuts, seeds, and butter and lower intake of fruit and low-fat yogurt; DP2 positively correlated with SFAs (r = 0.76) and negatively with PUFAs (r = -0.64) and MUFAs (r = -0.01), characterized by higher intake of butter and high-fat cheese and lower intake of nuts and seeds. Only DP2 was associated with higher obesity and abdominal obesity incidence (OR: 1.24; 95% CI: 1.02, 1.45; and OR: 1.19; 95% CI: 1.02, 1.38, respectively). Neither of the dietary patterns was associated with T2D incidence. CONCLUSIONS: These findings provide evidence that a dietary pattern characterized by higher SFA and lower PUFA foods is associated with obesity and abdominal obesity incidence, but not T2D.

High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men.

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (-25%, -27%, and -46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (-37%, -46%, and -64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction (R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial.

Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic-euglycaemic clamp.

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic-euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin-stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin-resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially-with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides-compared to the hyperinsulinaemic-euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids.

AIMS/HYPOTHESIS: This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. METHODS: Non-obese (BMI < 30 kg/m2) adults aged 18-35 years (N = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses. RESULTS: Thirteen per cent of individuals had impaired fasting glucose (IFG; n = 14) or impaired glucose tolerance (IGT; n = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m2) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT. CONCLUSIONS/INTERPRETATION: Hyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.

Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5n-3DPA (RvD5n-3DPA) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E2 (15-keto-PGE2). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

Short update on docosapentaenoic acid: a bioactive long-chain n-3 fatty acid.

PURPOSE OF REVIEW: Docosapentaenoic acid (DPA) is a long-chain n-3 polyunsaturated fatty acid that is intermediary between eicosapentaenoic acid and docosahexaenoic acid in the n-3 synthesis pathway. DPA is part of our normal diet through fish and lean red meat. In recent years, DPA has received increasing attention as an important bioactive fatty acid in light of its potential beneficial health effects, which include anti-inflammatory actions, antiplatelet aggregation, and improved plasma lipid prolife. This review provides a short summary of the most recent research on DPA. RECENT FINDINGS: In this review, we report on the latest association data as well as data generated from in-vitro and in-vivo studies on DPA and cardiovascular health, mental health, inflammation, and cancer. We also report on the newly identified DPA metabolites and their effects on exacerbation of inflammation in animal models. SUMMARY: Although there is a growing body of evidence supporting DPA's role as an important bioactive fatty acid, there is a need for more 'cause and effect studies', clinical trials and studies which can reveal whether DPA plays separate roles to those identified for eicosapentaenoic acid and docosahexaenoic acid.

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model.

In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep (n = 7). Sheep were familiarized to treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up to 4.4 km/h). A second HEC was conducted ∼18 h after the acute exercise. Musculus semimembranosus biopsies were obtained before and after each HEC. Glucose infusion rate during the HEC increased 40% (P = 0.003) and insulin sensitivity (glucose infusion rate/plasma insulin concentration) increased 32% (P = 0.028) after acute exercise. Activation of proximal insulin signaling in skeletal muscle after the HEC, measured as Ser(473) phosphorylation of Akt, increased approximately five-fold in response to insulin (P < 0.001) and was unaltered by acute exercise performed 18 h earlier. PGC1α and GLUT4 protein, glycogen content and citrate synthase activity in skeletal muscle did not change in response to insulin or exercise. In conclusion, improved insulin sensitivity and unchanged proximal insulin signaling on the day after acute exercise in sheep are consistent with responses in humans and rodents, suggesting that the sheep is an appropriate large-animal model in which to study responses to exercise.

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction.

Individuals born after intrauterine growth restriction (IUGR) are at an increased risk of developing diabetes in their adult life. IUGR impairs ß-cell function and reduces ß-cell mass, thereby diminishing insulin secretion. IUGR also induces insulin resistance, with impaired insulin signaling in muscle in adult humans who were small for gestational age (SGA) and in rodent models of IUGR. There is epidemiological evidence in humans that exercise in adults can reduce the risk of metabolic disease following IUGR. However, it is not clear whether adult IUGR individuals benefit to the same extent from exercise as do normal-birth-weight individuals, as our rat studies suggest less of a benefit in those born IUGR. Importantly, however, there is some evidence from studies in rats that exercise in early life might be able to reverse or reprogram the long-term metabolic effects of IUGR. Studies are needed to address gaps in current knowledge, including determining the mechanisms involved in the reprogramming effects of early exercise in rats, whether exercise early in life or in adulthood has similar beneficial metabolic effects in larger animal models in which insulin resistance develops after IUGR. Human studies are also needed to determine whether exercise training improves insulin secretion and insulin sensitivity to the same extent in IUGR adults as in control populations. Such investigations will have implications for customizing the recommended level and timing of exercise to improve metabolic health after IUGR.

Orally administered [¹4C]DPA and [¹4C]DHA are metabolised differently to [¹4C]EPA in rats.

Previous studies have revealed that C20 PUFA are significantly less oxidised to CO2 in whole-body studies compared with SFA, MUFA and C18 PUFA. The present study determined the extent to which three long-chain PUFA, namely 20:5n-3 EPA, 22:5n-3 docosapentaenoic acid (DPA) and 22:6n-3 DHA, were catabolised to CO2 or, conversely, incorporated into tissue lipids. Rats were administered a single oral dose of 2·5 µCi [1-¹4C]DPA, [1-¹4C]EPA, [1-¹4C]DHA or [1-¹4C]oleic acid (18:1n-9; OA), and were placed in a metabolism chamber for 6 h where exhaled ¹4CO2 was trapped and counted for radioactivity. Rats were euthanised after 24 h and tissues were removed for analysis of radioactivity in tissue lipids. The results showed that DPA and DHA were catabolised to CO2 significantly less compared with EPA and OA (P<0·05). The phospholipid (PL) fraction was the most labelled for all three n-3 PUFA compared with OA in all tissues, and there was no difference between C20 and C22 n-3 PUFA in the proportion of label in the PL fraction. The DHA and DPA groups showed significantly more label than the EPA group in both skeletal muscle and heart. In the brain and heart tissue, there was significantly less label in the cholesterol fraction from the C22 n-3 PUFA group compared with the C20 n-3 PUFA group. The higher incorporation of DHA and DPA into the heart and skeletal muscle, compared with EPA, suggests that these C22 n-3 PUFA might play an important role in these tissues.

A short-term n-3 DPA supplementation study in humans.

PURPOSE: Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids. METHODS: Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood samples were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids. RESULTS: Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns. CONCLUSION: The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.

Novel approach to investigate the association between type 2 diabetes risk and dietary fats in a dietary pattern context: a scoping review.

The effect of dietary fat on type 2 diabetes (T2D) risk is unclear. A posteriori dietary pattern methods have been increasingly used to investigate how dietary fats impact T2D risk. However, the diverse nutrients, foods and dietary patterns reported in these studies requires examination to better understand the role of dietary fats. This scoping review aimed to systematically search and synthesize the literature regarding the association between dietary patterns characterized by dietary fats and T2D risk using reduced rank regression. Medline and Embase were searched for cross-sectional, cohort or case-control studies published in English. Of the included studies (n = 8), five high-fat dietary patterns, mostly high in SFA, were associated with higher T2D risk or fasting glucose, insulin and Homeostasis Model Assessment (HOMA) levels. These were mostly low-fiber (n = 5) and high energy-density (n = 3) dietary patterns characterized by low fruit and vegetables intake, reduced fat dairy products and higher processed meats and butter intake. Findings from this review suggest that a posteriori dietary patterns high in SFA that increase T2D risk are often accompanied by lower fruits, vegetables and other fiber-rich foods intake. Therefore, healthy dietary fats consumption for T2D prevention should be encouraged as part of a healthful dietary pattern.

Longitudinal Associations Between Fat-Derived Dietary Patterns and Early Markers of Cardiovascular Disease Risk in the UK Biobank Study.

Background Although the impact of dietary fats on cardiovascular disease (CVD) risk is widely researched, longitudinal associations between dietary patterns (DPs) based on fat type and early markers of CVD risk remain unclear. Methods and Results UK Biobank participants (46.9% men, mean age 55 years) with data on early markers of CVD risk (n=12 706) were followed longitudinally (2014-2020; mean 8.4 years). Two DPs (DP1, DP2) were derived using reduced rank regression (response variables: monounsaturated fat, polyunsaturated fat, and saturated fat based on two 24-hour dietary assessments. Multivariable logistic and linear regression were used to investigate associations between DPs and odds of elevated CVD risk (using the nonlaboratory Framingham Risk Score) and changes in early CVD markers, respectively. DP1 (characterized by higher nuts and seeds and lower fruit and legumes intake) was positively correlated with saturated fat, monounsaturated fat, and polyunsaturated fat; DP2 (characterized by higher butter and high-fat cheese, lower nuts and seeds intake) was positively correlated with saturated fat and negatively with polyunsaturated fat and monounsaturated fat. DP2 was associated with slightly higher odds of elevated CVD risk (odds ratio, 1.04 [95% CI, 1.00-1.07]). DP1 was associated with higher diastolic blood pressure (ß, 0.20 [95% CI, 0.01-0.37]) and lower cardiac index (ß, -0.02 [95% CI, -0.04 to -0.01]); DP2 was associated with higher carotid intima medial thickness (ß, 1.80 [95% CI, 0.01-3.59]) and lower left ventricular ejection fraction (ß, -0.15 [95% CI, -0.24 to -0.07]) and cardiac index (ß, -0.01 [95% CI, -0.02 to -0.01]). Conclusions This study suggests small but statistically significant associations between DPs based on fat type and some early markers of CVD risk. Further research is needed to confirm these associations.

Is vascular insulin resistance an early step in diet-induced whole-body insulin resistance?

There is increasing evidence that skeletal muscle microvascular (capillary) blood flow plays an important role in glucose metabolism by increasing the delivery of glucose and insulin to the myocytes. This process is impaired in insulin-resistant individuals. Studies suggest that in diet-induced insulin-resistant rodents, insulin-mediated skeletal muscle microvascular blood flow is impaired post-short-term high fat feeding, and this occurs before the development of myocyte or whole-body insulin resistance. These data suggest that impaired skeletal muscle microvascular blood flow is an early vascular step before the onset of insulin resistance. However, evidence of this is still lacking in humans. In this review, we summarise what is known about short-term high-calorie and/or high-fat feeding in humans. We also explore selected animal studies to identify potential mechanisms. We discuss future directions aimed at better understanding the 'early' vascular mechanisms that lead to insulin resistance as this will provide the opportunity for much earlier screening and timing of intervention to assist in preventing type 2 diabetes.

Whole-Body Vibration Stimulates Microvascular Blood Flow in Skeletal Muscle.

PURPOSE: Whole-body vibration (WBV) therapy has been reported to potentially act as an exercise mimetic by improving muscle function and exercise capacity in a variety of healthy and clinical populations. Considering the important role that microvascular blood flow plays in muscle metabolism and exercise capacity, we investigated the muscle microvascular responses of acute WBV to knee extension exercise (KEX) in healthy individuals. METHODS: Eleven healthy adults (age: 33 ± 2 yr; body mass index: 23.6 ± 1.1 kg·m-2) underwent 3 min of WBV, or 3 min of KEX at 25% of one-repetition maximum, in a randomized order separated by a minimum of 72 h. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh muscle microvascular blood flow was measured via contrast-enhanced ultrasound at baseline and throughout the 3-min postintervention recovery period. RESULTS: Both WBV and KEX significantly increased peak microvascular blood flow (WBV, 5.6-fold; KEX, 21-fold; both P < 0.05) during the 3-min recovery period. Despite a similar increase in femoral arterial blood flow (~4-fold; both P < 0.05 vs baseline) and whole-body oxygen consumption measured by indirect calorimetry (WBV, 48%; KEX, 60%; both P < 0.05 vs baseline) in both conditions, microvascular blood flow was stimulated to a greater extent after KEX. CONCLUSION: A single 3-min session of WBV in healthy individuals is sufficient to significantly enhance muscle microvascular blood flow. Despite KEX providing a more potent stimulus, WBV may be an effective method for improving microvascular blood flow in populations reported to exhibit microvascular dysfunction such as patients with type 2 diabetes.

Farmed Mussels: A Nutritive Protein Source, Rich in Omega-3 Fatty Acids, with a Low Environmental Footprint.

The world's ever-growing population presents a major challenge in providing sustainable food options and in reducing pressures on the Earth's agricultural land and freshwater resources. Current estimates suggest that agriculture contributes ~30% of global greenhouse gas (GHG) emissions. Additionally, there is an increased demand for animal protein, the production of which is particularly polluting. Therefore, the climate-disrupting potential of feeding the planet is likely to substantially worsen in the future. Due to the nutritional value of animal-based protein, it is not a simple solution to recommend a wholesale reduction in production/consumption of animal proteins. Rather, employing strategies which result in the production of low carbon animal protein may be part of the solution to reduce the GHGs associated with our diets without compromising diet quality. We suggest that farmed mussels may present a partial solution to this dilemma. Mussel production has a relatively low GHG production and does not put undue pressure on land or fresh water supplies. By drawing comparisons to other protein sources using the Australian Food and Nutrient Database and other published data, we demonstrate that they are a sustainable source of high-quality protein, long-chain omega-3 fatty acids, phytosterols, and other key micronutrients such as B-12 and iron. The aim of this review is to summarise the current knowledge on the health benefits and potential risks of increasing the consumption of farmed mussels.

Short-term docosapentaenoic acid (22:5 n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats.

The metabolic fate of dietary n-3 docosapentaenoic acid (DPA) in mammals is currently unknown. The aim of the present study was to determine the extent of conversion of dietary DPA to DHA and EPA in rats. Four groups of male weanling Sprague-Dawley rats (aged 5 weeks) were given 50 mg of DPA, EPA, DHA or oleic acid, daily for 7 d by gavage. At the end of the treatment period, the tissues were analysed for concentrations of long-chain PUFA. DPA supplementation led to significant increases in DPA concentration in all tissues, with largest increase being in adipose (5-fold) and smallest increase being in brain (1.1-fold). DPA supplementation significantly increased the concentration of DHA in liver and the concentration of EPA in liver, heart and skeletal muscle, presumably by the process of retroconversion. EPA supplementation significantly increased the concentration of EPA and DPA in liver, heart and skeletal muscle and the DHA concentration in liver. DHA supplementation elevated the DHA levels in all tissues and EPA levels in the liver. Adipose was the main tissue site for accumulation of DPA, EPA and DHA. These data suggest that dietary DPA can be converted to DHA in the liver, in a short-term study, and that in addition it is partly retroconverted to EPA in liver, adipose, heart and skeletal muscle. Future studies should examine the physiological effect of DPA in tissues such as liver and heart.