title: The odd-carbon medium-chain fatty triglyceride triheptanoin does not reduce hepatic steatosis.
abstract: Non-alcoholic fatty-liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Previously, we showed that a high-protein diet minimized diet-induced development of fatty liver and even reversed pre-existing steatosis. A high-protein diet leads to amino-acid catabolism, which in turn causes anaplerosis of the tricarboxylic-acid (TCA) cycle. Therefore, we hypothesized that anaplerosis of the TCA cycle could be responsible for the high-protein diet-induced improvement of NAFLD by channeling amino acids into the TCA cycle. Next we considered that an efficient anaplerotic agent, the odd-carbon medium-chain triglyceride triheptanoin (TH), might have similar beneficial effects.
  
  
  
  C57BL/6J mice were fed low-fat (8en%) or high-fat (42en%) oleate-containing diets with or without 15en% TH for 3 weeks.
  
  
  
  TH treatment enhanced the hepatic capacity for fatty-acid oxidation by a selective increase in hepatic Ppara, Acox, and Cd36 expression, and a decline in plasma acetyl-carnitines. It also induced pyruvate cycling through an increased hepatic PCK1 protein concentration and it increased thermogenesis reflected by an increased Ucp2 mRNA content. TH, however, did not reduce hepatic lipid content.
  
  
  
  The comparison of the present effects of dietary triheptanoin with a previous study by our group on protein supplementation shows that the beneficial effects of the high-protein diet are not mimicked by TH. This argues against anaplerosis as the sole explanatory mechanism for the anti-steatotic effect of a high-protein diet.
authors.affiliation: Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands. Electronic address: tinecomhair@hotmail.com.
authors.forename: Tine M
authors.initials: TM
authors.lastname: Comhair
authors.affiliation: Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Garcia Caraballo
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands; School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands.
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.affiliation: Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: S Eleonore
authors.initials: SE
authors.lastname: Koehler
mesh_terms: D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002331:Carnitine / Q000097:blood; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D000073600:Diet, High-Protein; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology*; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D047493:PPAR alpha; D014280:Triglycerides; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C531010:triheptanoin; D002784:Cholesterol; D042962:Acyl-CoA Oxidase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D002331:Carnitine
keywords: Anaplerosis; Diet; Non-alcoholic fatty liver disease; Steatosis; Triheptanoin