Serum Nonesterified Fatty Acids and Incident Stroke: The CHS

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996–1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)‐6 polyunsaturated, n‐3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5‐year follow‐up period. Total n‐3 (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]) and n‐6 (HR, 1.32 [95% CI, 1.01–1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo‐γ‐linolenic acid (20:3n‐6) was associated with higher risk (HR, 1.29 [95% CI, 1.02–1.63]), whereas cis ‐7‐hexadecenoic acid (16:1n‐9 c ) and arachidonic acid (20:4n‐6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47–0.97]; HR, 0.81 [95% CI. 0.65–1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n‐3 subclass and dihomo‐γ‐linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Effect of a carbohydrase admixture in growing pigs fed wheat-based diets in thermoneutral and heat stress conditions

The efficacy of exogenous carbohydrases in pig diets has been suggested to depend on enzyme activity and dietary fiber composition, but recent evidence suggests other factors such as ambient temperature might be important as well. Therefore, we investigated the effect of heat stress (HS) on the efficacy of a multienzyme carbohydrase blend in growing pigs. Ninety-six (barrows: gilts; 1:1) growing pigs with initial body weight (BW) of 20.15 ± 0.18 kg were randomly assigned to six treatments, with eight replicates of two pigs per pen in a 3 × 2 factorial arrangement: three levels of carbohydrase (0, 1X, or 2X) at two environmental temperatures (20 °C or cyclical 28 °C nighttime and 35 °C day time). The 1X dose (50 g/tonne) provided 1,250 viscosimetry unit (visco-units) endo-β-1,4-xylanase, 4,600 units α-l-arabinofuranosidase and 860 visco-units endo-1,3(4)-β-glucanase per kilogram of feed. Pigs were fed ad libitum for 28 d and 1 pig per pen was sacrificed on day 28. There was no enzyme × temperature interaction on any response criteria; thus, only main effects are reported. Enzyme treatment quadratically increased (P < 0.05) BW on day 28, average daily gain (ADG) (P < 0.05), and average daily feed intake (ADFI) (P < 0.05) with the 1X level being highest. HS reduced the BW at day 14 (P < 0.01) and day 28 (P < 0.01), ADG (P < 0.01), and ADFI (P<0.001). There was a trend of increased feed efficiency (G:F) (P < 0.1) in the HS pigs. HS increased apparent jejunal digestibility of energy (P < 0.05) and apparent ileal digestibility of calcium (P < 0.01). At day 1, HS reduced serum glucose (P < 0.001) but increased nonesterified fatty acid (P < 0.01). In the jejunum, there was a trend of increased villi height by carbohydrases (P < 0.1), whereas HS reduced villi height (P < 0.05). HS increased the jejunal mRNA abundance of IL1β in the jejunum (P < 0.001). There was a trend for a reduction in ileal MUC2 (P < 0.1) and occludin (P < 0.1) by HS, and a trend for increased PEPT1 (P < 0.1). There was no effect of HS on alpha diversity and beta diversity of the fecal microbiome, but there was an increase in the abundance of pathogenic bacteria in the HS group. In conclusion, HS did not alter the efficacy of carbohydrases. This suggests that carbohydrases and HS modulate pig performance independently.

Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping

The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis but could also be contributed to by reduced adipose tissue (AT) dietary fatty acid (DFA) trapping and increased 'spillover' into the circulation. Thirty-one subjects with IGT (14 women, 17 men) and 29 with normal glucose tolerance (NGT, 15 women, 14 men) underwent a meal test with oral and intravenous palmitate tracers and the oral [18F]-fluoro-thia-heptadecanoic acid positron emission tomography method. Postprandial palmitate appearance (Rapalmitate) was higher in IGT vs. NGT (P < 0.001), driven exclusively by Rapalmitate from obesity-associated increase in intracellular lipolysis (P = 0.01), as Rapalmitate from DFA spillover was not different between the groups (P = 0.19) and visceral AT DFA trapping was even higher in IGT vs. NGT (P = 0.02). Plasma glycerol appearance was lower in IGT (P = 0.01), driven down by insulin resistance and increased insulin secretion. Thus, we found higher AT DFA trapping, limiting spillover to lean organs and in part offsetting the increase in Rapalmitate from intracellular lipolysis. Whether similar findings occur in frank diabetes, a condition also characterized by insulin resistance but relative insulin deficiency, requires further investigation (Clinicaltrials.gov: NCT04088344, NCT02808182).

100th Anniversary of the discovery of insulin Perspective: Insulin and Adipose Tissue Fatty Acid Metabolism

Insulin inhibits systemic nonesterified fatty acid (NEFA) flux to a greater degree than glucose or any other metabolite. This remarkable effect is mainly due to insulin-mediated inhibition of intracellular triglyceride (TG) lipolysis in adipose tissues and is essential to prevent diabetic ketoacidosis, but also to limit the potential lipotoxic effects of NEFA in lean tissues that contributes to the development of diabetes complications. Insulin also regulates adipose tissue fatty acid esterification, glycerol and TG synthesis, lipogenesis and possibly oxidation, contributing to the trapping of dietary fatty acids in the postprandial state. Excess NEFA flux at a given insulin level has been used to define in vivo adipose tissue insulin resistance. Adipose tissue insulin resistance defined in this fashion has been associated with several dysmetabolic features and complications of diabetes, but the mechanistic significance of this concept is not fully understood. This review focusses on the in vivo regulation of adipose tissue fatty acid metabolism by insulin and the mechanistic significance of the current definition of adipose tissue insulin resistance. One hundred years after the discovery of insulin and despite decades of investigations, much is still to be understood about the multifaceted in vivo actions of this hormone on adipose tissue fatty acid metabolism.

Changes in Expression of the Genes for the Leptin Signaling in Hypothalamic-Pituitary Selected Areas and Endocrine Responses to Long-Term Manipulation in Body Weight and Resistin in Ewes

Both long-term undernutrition and overnutrition disturb metabolic balance, which is mediated partially by the action of two adipokines, leptin and resistin (RSTN). In this study, we manipulated the diet of ewes to produce either a thin (lean) or fat (fat) body condition and investigated how RSTN affects endocrine and metabolic status under different leptin concentrations. Twenty ewes were distributed into four groups (n = 5): the lean and fat groups were administered with saline (Lean and Fat), while the Lean-R (Lean-Resistin treated) and Fat-R (Fat-Resistin treated) groups received recombinant bovine resistin. Plasma was assayed for LH, FSH, PRL, RSTN, leptin, GH, glucose, insulin, total cholesterol, nonesterified fatty acid (NEFA), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Expression levels of a suppressor of cytokine signaling (SOCS-3) and the long form of the leptin receptor (LRb) were determined in selected brain regions, such as the anterior pituitary, hypothalamic arcuate nucleus, preoptic area and ventro- and dorsomedial nuclei. The results indicate long-term alterations in body weight affect RSTN-mediated effects on metabolic and reproductive hormones concentrations and the expression of leptin signaling components: LRb and SOCS-3. This may be an adaptive mechanism to long-term changes in adiposity during the state of long-day leptin resistance.

3-Amino-1,2,4-Triazole Induces Quick and Strong Fat Loss in Mice with High Fat-Induced Metabolic Syndrome

Background. Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS. Methods. Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg-1·24 h-1) for 12 weeks. Results. The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels. Conclusions. In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status.

Probiotic supplementation increases carbohydrate metabolism in trained male cyclists: a randomized, double-blind, placebo-controlled crossover trial

We hypothesized that probiotic supplementation (PRO) increases the absorption and oxidation of orally ingested maltodextrin during 2 h endurance cycling, thereby sparing muscle glycogen for a subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate oxidation, plasma metabolites and insulin, gastrointestinal (GI) permeability, and subjective symptoms of discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or placebo for 4 wk, separated by a 14-day washout period. After each period, cyclists consumed a 10% maltodextrin solution (initial 8 mL/kg bolus and 2 mL/kg every 15 min) while exercising for 2 h at 55% maximal aerobic power output, followed by a 100-kJ time trial. PRO resulted in small increases in peak oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs. 0.77 ± 0.09 g/min; P = 0.016) and mean total carbohydrate oxidation (2.20 ± 0.25 vs. 1.87 ± 0.39 g/min; P = 0.038), whereas fat oxidation was reduced (0.40 ± 0.11 vs. 0.55 ± 0.10 g/min; P = 0.021). During PRO, small but significant increases were seen in glucose absorption, plasma glucose, and insulin concentration and decreases in nonesterified fatty acid and glycerol. Differences between markers of GI damage and permeability and time-trial performance were not significant ( P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, whereas having no effect on subsequent time-trial performance.

Effects of corn supplementation and age on performance and reproduction of beef females grazing lush spring pasture

This study evaluated how corn supplementation and age of female affected body weight (BW), body condition score (BCS), artificial insemination (AI) pregnancy rate, and blood metabolites (nonesterified fatty acid [NEFA], β-hydroxybutyrate [BHBA], and blood urea nitrogen [BUN]) when grazing lush spring pasture. Angus and Angus × Simmental beef females (n = 361) were blocked by location, stratified by BW and BCS, and then were assigned to groups (n = 8 groups/treatment combination; 9–14 females/group). The study utilized a stratified, randomized complete block design with a 2 × 2 factorial arrangement of treatments. The four treatment combinations were: yearling heifers receiving no supplement (CON-H); yearling heifers receiving supplement of dry-rolled corn (SUPP-H; 1.81 kg as-fed/heifer/d) for 42 d; 2-yr-old lactating cow-calf pairs receiving no supplement (CON-C); and 2-yr-old lactating cow-calf pairs receiving supplement of dry-rolled corn (SUPP-C; 1.81 kg as-fed/cow/d) for 42 d. Supplementation began at AI (end of April) when cows began grazing tall fescue (Festuca arundinacea schreb)-red clover (Trifolium pratense) pastures. Pasture forage was collected weekly for analysis. Throughout the study, forage crude protein decreased (P &lt; 0.01) over time, but acid detergent fiber (ADF), neutral detergent fiber, dry matter, forage height, and forage mass all increased (P &lt; 0.01) over time. Females receiving SUPP tended (P = 0.10) to have greater BW and greater BW change over the supplementation period. Supplementation × age effects for BCS were detected (P = 0.04); SUPP-H had greater BCS than all other treatment combinations at d 42. Cow BHBA was greater (P &lt; 0.01) compared with heifers. Female NEFA increased (P &lt; 0.01) from d 12 to 42. Control females had greater (P = 0.02) serum NEFA concentrations compared with SUPP females. Control females had greater (P = 0.03) BUN concentrations compared with SUPP females. Cow BUN was greater (P &lt; 0.01) than heifer BUN. Supplementation effects were not detected (P ≥ 0.25) for AI or overall pregnancy rate. In conclusion, there were no supplementation × age interactions excluding d 42 BCS. Supplementation regardless of female age tended to improve d 42 BW and BW change. Cow BHBA and BUN was greater compared with the heifers, whereas the supplemented females had decreased NEFA and BUN. Cows tended to have greater AI pregnancy rates than heifers, but supplementation did not affect AI or overall pregnancy rates.