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.

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.

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.

OLI is a physiological repressor of systemic resistin release whereas FFA upregulate resistin release in vitro from adipocytes.

No abstract