Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels.

Short-term Regulation of Resistin in vivo by Oral Lipid Ingestion and in vitro by Fatty Acid Stimulation.

BACKGROUND AND AIM: Dysbalance of pro- and anti-inflammatory adipokines is a hallmark of metabolic syndrome but their nutrition-dependent regulation in healthy individuals is poorly characterized. We investigated pro-inflammatory resistin and anti-inflammatory adiponectin regulation during oral lipid ingestion (OLI) in healthy adults. Response of resistin upon free fatty acid (FFA) stimulation was investigated in 3T3-L1 adipocytes. MATERIAL AND METHODS: 100 healthy volunteers underwent OLI. Venous blood was drawn after 0, 2, 4, and 6 hours (h). Subjects were characterized by anthropometric and standard laboratory parameters. Serum concentrations of adiponectin and resistin were measured by enzyme-linked immunosorbent assay (ELISA). Adipocytes were stimulated with FFA and concentrations of adipokines were measured by ELISA. RESULTS: Irrespective of BMI and gender, OLI led to a significant reduction of resistin serum levels in a stepwise manner whereas adiponectin concentrations remained unchanged. There were positive correlations of resistin with waist/hip ratio and visfatin levels, as was calculated by regression analysis. Resistin concentrations were significantly higher in smokers when compared to non-smokers. Adiponectin concentrations were higher in females and in users of hormonal contraception. Adiponectin levels showed a positive correlation with heart rate and HDL cholesterol and a negative correlation with age, waist/hip-ratio, BMI, diastolic/systolic blood pressure, visfatin levels and LDL/HDL-ratio. Resistin secretion was significantly induced by palmitic acid, linoleic acid and oleic acid in adipocytes. CONCLUSIONS: OLI is a physiological repressor of systemic resistin release whereas FFA upregulate resistin release in vitro from adipocytes.

Short-term and divergent regulation of FGF-19 and FGF-21 during oral lipid tolerance test but not oral glucose tolerance test.

CONTEXT: Regulation of FGF-19 and FGF-21 by oral uptake of lipids and carbohydrates in healthy individuals is poorly characterized. OBJECTIVE: We investigated the regulation of FGF-19 and FGF-21 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100). DESIGN AND SETTING: 100 volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 h (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a special OLTT solution was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of FGF-19 and FGF-21 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean FGF-19 levels ranged between 12 and 544 pg/ml with a fasting mean value of 105±81 pg/ml and 118±86 pg/ml in OLTT and OGTT. Mean FGF-21 levels ranged between 4 and 1 393 pg/ml with a fasting mean value of 160±204 pg/ml and 235±288 pg/ml in OLTT and OGTT. There was a significant, positive correlation between FGF-19 and FGF-21 in OLTT (p<0.001, r=0.5) and in OGTT (p=0.011, r=0.4). FGF-21 levels were positively correlated with waist circumference and waist hip-ratio in both cohorts. OGTT had no effect on FGF-19 and FGF-21. In contrast, FGF-19 levels were significantly induced and FGF-21 levels were significantly reduced during OLTT. CONCLUSIONS: OLTT is a physiological inductor of FGF-19 and a repressor of FGF-21 in healthy adults. There is a significant and positive correlation between FGF-19 and FGF-21. Dietary lipids specifically and differentially regulate FGF-19 and FGF-21 whereas dietary carbohydrates have no effect. The present data provide the clinical basis for the postulated negative feedback loop between dietary lipids and postprandial inhibition of hepatic lipogenesis.

Serum progranulin concentrations are not responsive during oral lipid tolerance test and oral glucose tolerance test.

The postprandial regulation of progranulin by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of progranulin in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of progranulin were measured by enzyme-linked immunosorbent assay (ELISA). Circulating progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin levels ranged between 31.3±8.7 and 40.6±7.7 ng/ml and were not different in subgroups addressing BMI, gender, family history, smoking habits, and hormonal contraception. There was a reciprocal correlation of progranulin with HDL (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and postprandial circulating progranulin levels are not different in BMI subgroups. Oral uptake of carbohydrates and lipids does not influence circulating progranulin levels in a short-term manner. A postprandial and short-term regulation of this adipokine is absent, at least in healthy subjects. There is a negative correlation of progranulin with HDL cholesterol, but a positive correlation with LDL cholesterol. This reciprocal association might be of physiological importance for an individual's atherosclerotic risk.

Short-term regulation of Visfatin release in vivo by oral lipid ingestion and in vitro by fatty acid stimulation.

Visfatin represents a new adipokine secreted by visceral adipose tissue and possibly regulating insulin sensitivity. Data on the regulation of visfatin are sparse and contradictory. Our study investigates the regulation of serum visfatin concentrations in healthy and non-diabetic subjects in response to the ingestion of a newly developed oral lipid solution (OLI) in vivo. Furthermore, the effects of a broad spectrum of fatty acids on adipocytic visfatin release were investigated in vitro.100 (42 male and 58 female) healthy volunteers were included in the study. Anthropometric and laboratory parameters (lipoproteins, glucose, insulin, C-peptide) were measured after an overnight fast at 0 h and 2 h, 4 h, and 6 h after OLI. 3T3-L1 preadipocytes were differentiated into mature adipocytes and stimulated with increasing doses of 10 different fatty acids, and the release of visfatin into the supernatants was measured by ELISA.Serum triglycerides significantly rose after OLI. This was accompanied by a significant decrease of glucose, insulin and C-peptide. Serum visfatin levels significantly decreased after OLI. Fasting visfatin levels were negatively correlated with fasting glucose levels. Of the 5 saturated fatty acids tested, only palmitic acid exerted significant effects by strongly downregulating visfatin release by about 66%. The mono-unsaturated fatty acids palmitoleic acid and oleic acid exerted opposite effects decreasing/increasing visfatin release, respectively. Both of the poly-unsaturated fatty acids linoleic acid and arachidonic acid decreased visfatin release.Oral lipid ingestion is a physiological regulator of systemic visfatin release. Fatty acids differentially regulate visfatin release in vitro.