title: Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates.
abstract: Non-alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.
  
  
  OBJECTIVE
  To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity.
  
  
  METHODS
  Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance.
  
  
  RESULTS
  Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons.
  
  
  CONCLUSIONS
  Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.
authors: Department of Medicine/Division of Diabetes. The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors: Subhash
authors: S
authors: Kamath
authors: Alberto O
authors: AO
authors: Chavez
authors: Amalia
authors: A
authors: Gastaldelli
authors: Francesca
authors: F
authors: Casiraghi
authors: Glenn A
authors: GA
authors: Halff
authors: Gregory A
authors: GA
authors: Abrahamian
authors: Alberto M
authors: AM
authors: Davalli
authors: Raul A
authors: RA
authors: Bastarrachea
authors: Anthony G
authors: AG
authors: Comuzzie
authors: Rodolfo
authors: R
authors: Guardado-Mendoza
authors: Lilia M
authors: LM
authors: Jimenez-Ceja
authors: Vicki
authors: V
authors: Mattern
authors: Ana Maria
authors: AM
authors: Paez
authors: Andrea
authors: A
authors: Ricotti
authors: Mary E
authors: ME
authors: Tejero
authors: Paul B
authors: PB
authors: Higgins
authors: Iram Pablo
authors: IP
authors: Rodriguez-Sanchez
authors: Devjit
authors: D
authors: Tripathy
authors: Ralph A
authors: RA
authors: DeFronzo
authors: Edward J
authors: EJ
authors: Dick
authors: Gary W
authors: GW
authors: Cline
authors: Franco
authors: F
authors: Folli
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D016014:Linear Models; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D010215:Papio; D021241:Spectrometry, Mass, Electrospray Ionization; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; D005947:Glucose