Determination of natural antibodies, beta-hydroxybutyric acid, and non-esterified fatty acid levels in the serum of peripartum Tuj and Hemşin sheep

Background and Aim: Many metabolic and immunological changes occur during the transition period. Innate immunity plays an important role against to infections and natural antibodies (NAb) are important in immunity. This study aims to determine a connection between serum NAb titers, beta-hydroxybutyric acid (BHBA), and non-esterified fatty acid (NEFA) concentrations in Tuj and Hemsin sheep during the peripartum period. Materials and Methods: Serum NAb, BHBA, and NEFA levels were determined from the blood samples collected from Tuj and Hemsin sheep on days 30 and 15 before birth, on the day of birth (day 0), and on days 15 and 30 after birth. Results: NAb titers were found to be higher in Tuj than in Hemsin sheep (p<0.001). No statistically significant difference was found in serum BHBA concentrations of both breeds on all sampling days (p>0.05). The serum NEFA level was lower in Tuj sheep in the last 15 days of pregnancy compared to Hemsin sheep (p<0.05), while no difference was found in samples collected at the other time points. Conclusion: This study indicated that serum NAb titers significantly changed in Tuj and Hemsin sheep during the transition period. Serum BHBA and NEFA concentrations increased during the last stages of pregnancy and decreased after birth. Based on these findings, it is suggested that the immunological status could vary by the breed of sheep or various factors that affect the sheep's metabolic state.

Association between breakfast skipping and postprandial hyperglycaemia after lunch in healthy young individuals

Breakfast skipping has become an increasing trend in the modern lifestyle and may play a role in obesity and type 2 diabetes. In our previous studies in healthy young individuals, a single incident of breakfast skipping increased the overall 24-h blood glucose and elevated the postprandial glycaemic response after lunch; however, it was difficult to determine whether this response was due to breakfast omission or the extra energy (i.e. lunch plus breakfast contents). The present study aimed to assess the postprandial glycaemic response and to measure their hormone levels when healthy young individuals had identical lunch and dinner, and the 24-h average blood glucose as a secondary outcome. Nine healthy young men (19−24 years) participated in two-meal trials: with breakfast (three-meal condition) or without breakfast (breakfast skipping condition). During the meals, each individual’s blood glucose was continuously monitored. Skipping breakfast resulted in a significantly higher (P &lt; 0·001) glycaemic response after lunch as compared with the glycaemic response after an identical lunch when breakfast was consumed. Despite the difference in the total energy intake, the 24-h average blood glucose was similar between the two-meal conditions (P = 0·179). Plasma NEFA level was significantly higher (P &lt; 0·05) after lunch when breakfast was omitted, and NEFA level positively correlated with the postprandial glycaemic response (r 0·631, P &lt; 0·01). In conclusion, a single incident of breakfast skipping increases postprandial hyperglycaemia, and associated impaired insulin response, after lunch. The present study showed that skipping breakfast influences glucose regulation even in healthy young individuals.

Modulation of Adipocytokines Production and Serum NEFA Level by Metformin, Glimepiride, and Sitagliptin in HFD/STZ Diabetic Rats

Type 2 diabetes mellitus (T2DM) is a group of metabolic disorders characterized by hyperglycemia owing to insulin resistance and/or insulin deficiency. Current theories of T2DM pathophysiology include a decline inβ-cells function, a defect in insulin signaling pathways, and a dysregulation of secretory function of adipocytes. This study aimed to investigate the effect of different antidiabetic drugs on serum levels of certain adipocytokines and nonesterified fatty acids (NEFA) in high-fat diet (HFD)/streptozotocin- (STZ-) induced diabetic rats. All treatments significantly decreased serum NEFA level. Metformin and sitagliptin increased serum adiponectin level, whereas they decreased serum leptin level. Glimepiride showed significant decline in serum levels of both adiponectin and leptin. All treatments remarkably ameliorated insulin resistance, suggested by an improvement of glycemic control, a significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR), and a correction in lipid profile. Modulation of adipocytokines production (i.e., increased serum adiponectin and decreased serum leptin) may also underlie the improvement of insulin resistance and could be a possible mechanism for the beneficial cardiovascular effects of metformin and sitagliptin.

Carbohydrate- and lipid-enriched meals acutely disrupt glycemic homeostasis by inducing transient insulin resistance in rats

Chronic intake of high-carbohydrate or high-lipid diets is a well-known insulin resistance inducer. This study investigates the immediate effect (1–6 h) of a carbohydrate- or lipid-enriched meal on insulin sensitivity. Fasted rats were refed with standard, carbohydrate-enriched (C), or lipid-enriched (L) meal. Plasma insulin, glucose, and non-esterified fatty acids (NEFA) were measured at 1, 2, 4, and 6 h of refeeding. The glucose–insulin index showed that either carbohydrates or lipids decreased insulin sensitivity at 2 h of refeeding. At this time point, insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) detected insulin resistance in C rats, while GTT confirmed it in L rats. Reduced glycogen and phosphorylated AKT and GSK3 content revealed hepatic insulin resistance in C rats. Reduced glucose uptake in skeletal muscle subjected to the fatty acid concentration that mimics the high NEFA level of L rats suggests insulin resistance in these animals is mainly in muscle. In conclusion, carbohydrate- or lipid-enriched meals acutely disrupt glycemic homeostasis, inducing a transient insulin resistance, which seems to involve liver and skeletal muscle, respectively. Thus, the insulin resistance observed when those types of diets are chronically consumed may be an evolution of repeated episodes of this transient insulin resistance.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28 ± 3 yr, body mass index: 27.2 ± 1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin + Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions ( P < 0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level ( P < 0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI ( P < 0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

The effect of Intralipid® infusion on the human leucocyte sodium-pump in vivo

1. The effect of unsaturated long-chain non-esterified fatty acids (NEFA) on the human leucocyte sodium-pump was studied in vivo.2. Plasma NEFA level was raised acutely from 0·28 (sd 0·10) to 2·54 (sd 0·48) mmol/l by infusion of ‘Intralipid 20%’ (trademark) at 90 ml/h with heparin, and the human leucocyte 22Na efflux rate constants were studied in eight normal weight males.3. After 3 h, there was a significant lowering of the total (from 3·97 (sd 0·92) to 3·10 (sd 0·71)/h; P < 0·01) and ouabain-sensitive 22Na efflux rate constants (from 2·89 (sd 0·55) to 2·37 (sd 0·62)/h; P < 0·02). Ouabain-insensitive efflux rate constants showed a tendency to fall (from 1·08 (sd 0·51) to 0·73 (sd 0·23)/h). Leucocyte potassium content remained unchanged, but sodium content rose from 31 (sd 12) to 38 (sd 18) mmol/kg dry weight (P < 0·05). Total, ouabain-insensitive and ouabain-sensitive efflux rates did not change significantly during the Intralipid-heparin infusion.4. Plasma insulin levels rose gradually throughout the 3 h infusion period.5. In conclusion, NEFA, when raised to pathological levels, can inhibit the leucocyte Na-pump in vivo even in the presence of physiological levels of serum albumin, and may increase insulin secretion.

Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

In the 7-day fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (Rd) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in Rd. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon ("hormone replacement"), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion ("hormone replacement + NEFA"). Glucose turnover was assessed using [3-3H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. Rd was constant during saline infusion, increased in the hormone replacement protocol, but was constant in the hormone replacement plus NEFA protocol. After a prolonged fast in the dog, 1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and 2) this decrease in the NEFA level causes an increase in Rd.

A Comparison of Gas-Liquid Chromatography and a Titration Method for the Determination of Plasma Non-Esterified Fatty Acid Levels during Pregnancy

The level of plasma non-esterified fatty acids (NEFA) was measured by gas-liquid chromatography (GLC) and a titration method in 194 samples collected during pregnancy and from four days to 24 weeks post partum. Both techniques indicated a similar pattern of changes in plasma NEFA associated with pregnancy. The titration estimates of NEFA level were usually greater than those measured by GLC, and there was some suggestion that the disparity between the methods was increased at the end of pregnancy and was reduced at six weeks after delivery.

Plasma non-esterified fatty acids in sheep

Concentrations of plasma non-esterified fatty acids (NEFA) in sheep were found to be within the range 0.1–0.9 m-equiv/l. Relatively high levels (1.0–2.5 m-equiv/l) occurred in pregnant and non-pregnant sheep when fasted. Intravenous injection of glucose (1.0 g/kg body wt.) depressed KEFA concentrations to levels of about 0.05 m-equiv/l. Insulin, injected intravenously, caused an initial fall in the NEFA level, followed by a sharp rise which was maintained throughout hypoglycaemia. These results suggest that in sheep, as in many other species, NEBA are of major metabolic importance.