title: Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis.
abstract: The spectrum of lipid-induced changes in the 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 short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours.
  
  
  
  Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured.
  
  
  
  Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration.
  
  
  
  Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract-secreted molecules important in glucose and energy homeostasis such as glucagon, incretins, and peptide YY.
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Vamvini
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Ole-Petter
authors.initials: OP
authors.lastname: Hamnvik
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Ayse
authors.initials: A
authors.lastname: Sahin-Efe
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Anna
authors.initials: A
authors.lastname: Gavrieli
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Fadime
authors.initials: F
authors.lastname: Dincer
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Farr
authors.affiliation: Division of Endocrinology (M.T.V., O.-P.H., A.S.-E., A.G., F.D., O.M.F., C.S.M.), Beth-Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts 02215; Department of Internal Medicine (M.T.V.), Mt Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts 02138; and Division of Endocrinology, Diabetes, and Hypertension (O.-P.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02054.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D052242:Adiponectin / Q000097:blood; D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D016207:Cytokines / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D005353:Fibronectins / Q000097:blood; D058851:GPI-Linked Proteins / Q000097:blood; D054439:Ghrelin / Q000097:blood; D005934:Glucagon / Q000097:blood; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D054795:Incretins / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D037102:Lectins / Q000097:blood; D008055:Lipids / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019894:Peptide YY / Q000097:blood; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D016207:Cytokines; C577593:FNDC5 protein, human; D005230:Fatty Acids, Nonesterified; D005353:Fibronectins; D058851:GPI-Linked Proteins; D054439:Ghrelin; C432397:ITLN1 protein, human; D054795:Incretins; D007328:Insulin; D037102:Lectins; D008055:Lipids; D060749:alpha-2-HS-Glycoprotein; C414620:fibroblast growth factor 21; D019894:Peptide YY; D005346:Fibroblast Growth Factors; D005934:Glucagon