title: In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity.
abstract: OBJECTIVE
  Free fatty acids (FFAs) cause insulin resistance and are often elevated in obesity. Chronic ingestion of diets rich in saturated fat induces more insulin resistance than diets rich in unsaturated fat, however, it remains unclear whether different FFAs cause distinct levels of insulin resistance in the short-term, which is relevant to the feeding and fasting cycle. Protein kinase C (PKC)-δ is implicated in hepatic insulin resistance. Therefore, we investigated the effects of short-term elevation of fatty acids with different degrees of unsaturation on hepatic insulin action and liver PKC-δ membrane translocation, a marker of activation.
  
  
  METHODS
  Triglyceride emulsions of Soybean Oil+Heparin (polyunsaturated (POLY)), Olive Oil+Heparin (monounsaturated (MONO)), Lard Oil+Heparin (saturated (SATU)), or saline (SAL) were infused intravenously for 7h to elevate plasma FFA concentrations ~3-4 fold in rats. During the last 2h of infusion, a hyperinsulinemic-euglycemic clamp with tritiated glucose methodology was performed to examine hepatic and peripheral insulin sensitivity.
  
  
  RESULTS
  Surprisingly, SATU, MONO, and POLY impaired peripheral insulin sensitivity (glucose utilization divided by insulin) to a similar extent. Furthermore, all lipids induced a similar degree of hepatic insulin resistance compared to SAL. Although there were changes in hepatic content of lipid metabolites, there were no significant differences in liver PKC-δ membrane translocation across fat groups.
  
  
  CONCLUSIONS
  In summary, in the short-term, FFAs with different degrees of unsaturation impair peripheral insulin sensitivity and induce hepatic insulin resistance as well as hepatic PKC-δ translocation to the same extent.
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: sandra.pereira@mail.utoronto.ca.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pereira
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: dbreensawatzky@gmail.com.
authors.forename: Danna M
authors.initials: DM
authors.lastname: Breen
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: anthony.naassan@gmail.com.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Naassan
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: shyuron@hotmail.com.
authors.forename: Penny Y T
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: h.uchino@med.toho-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchino
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Department of Medicine, University of Toronto, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada. Electronic address: gfantus@mtsinai.on.ca.
authors.forename: I George
authors.initials: IG
authors.lastname: Fantus
authors.affiliation: Department of Medicine, Division of Endocrinology, Université de Sherbrooke, 3001-12(e) Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada. Electronic address: andre.carpentier@usherbrooke.ca.
authors.forename: André C
authors.initials: AC
authors.lastname: Carpentier
authors.affiliation: Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Electronic address: roger.gutierrez@einstein.yu.edu.
authors.forename: Roger
authors.initials: R
authors.lastname: Gutierrez-Juarez
authors.affiliation: Department of Biochemistry, Signal Transduction Research Group, University of Alberta, 357 Heritage Medical Research Center, Edmonton, AB, T6G 2S2, Canada. Electronic address: david.brindley@ualberta.ca.
authors.forename: David N
authors.initials: DN
authors.lastname: Brindley
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: tlam@uhnresearch.ca.
authors.forename: Tony K T
authors.initials: TK
authors.lastname: Lam
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Department of Medicine, University of Toronto, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: adria.giacca@utoronto.ca.
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism; D004789:Enzyme Activation; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids / Q000009:adverse effects / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D000069463:Olive Oil; D010938:Plant Oils / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D017208:Rats, Wistar; D013024:Soybean Oil / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D000069463:Olive Oil; D010938:Plant Oils; D013024:Soybean Oil; C497260:Prkcd protein, rat; D051745:Protein Kinase C-delta; C029310:lard
keywords: Fat; Hyperinsulinemic–euglycemic clamp; Liver