Abstract


The spectrum of lipid-induced changes in secretion of hormones important in energy homeostasis has not yet been fully elucidated. To identify potential incretin-like effects in response to lipid administration, we examined the effect of intravenous (IV) vs. oral lipids on key molecules for energy homeostasis. After a 10 hour overnight fast, 26 subjects were randomized to receive: an oral lipid load, a 10% IV lipid emulsion, designed to eventually result in circulating lipid levels similar to those achieved by oral lipid load, a 20% IV lipid emulsion, or an IV saline infusion. view more

The spectrum of lipid-induced changes in secretion of hormones important in energy homeostasis has not yet been fully elucidated. To identify potential incretin-like effects in response to lipid administration, we examined the effect of intravenous (IV) vs. oral lipids on key molecules for energy homeostasis. After a 10 hour overnight fast, 26 subjects were randomized to receive: an oral lipid load, a 10% IV lipid emulsion, designed to eventually result in circulating lipid levels similar to those achieved by oral lipid load, a 20% IV lipid emulsion, or an IV saline infusion. Blood samples were obtained at 30 minutes intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Using ELISA and RIA based assays we measured the circulating levels of insulin, glucose, c-peptide, FFA, incretins (GLP-1, GIP), glucagon, PYY and ghrelin. We also measured the levels of other novel hepatokines, myokines and adipokines such as FGF-21,fetuin A, irisin, omentin and adiponectin. We found that oral lipid ingestion resulted in higher GLP-1, GIP, glucagon, and PYY levels compared to the other three groups (iAUC p= 0.003, p<0.001, p<0.001 and p<0.001, respectively). The 20% lipid emulsion, leading to higher FFA levels, resulted in greater insulin, c-peptide, and FGF-21 responses compared to placebo and/or the other two groups including the 10% lipid emulsion (iAUC p=0.002, p=0.005, p<0.001 and p<0.001, respectively). Omentin, adiponectin, fetuin A and irisin levels were not affected by either mode of lipid administration. We conclude that molecules important in glucose homeostasis such as insulin, c-peptide, glucagon and incretins, as well as energy homeostasis regulators such as PYY, exhibit a significant response to hyperlipidemia induced by oral lipids, probably through direct actions in the GI tract, highlighting that the route of lipid administration has a significant impact on metabolic regulation. Prolonged administration of intravenous lipids triggers hyperinsulinemia without concurrent decrease in glucose levels, a phenomenon observed in insulin resistant states. Other novel molecules important in energy homeostasis such as irisin, omentin and fetuin A remained unaffected by lipids.

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