title: Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans.
abstract: OBJECTIVE
  Previous studies have shown relationships between fatty acid ratios in adipose tissue triacylglycerol (TG), adipocyte size and measures of insulin sensitivity. We hypothesised that variations in adipose tissue de novo lipogenesis (DNL) in relation to adiposity might explain some of these observations.
  
  
  METHODS
  In a cross-sectional study, subcutaneous abdominal adipose tissue biopsies from 59 people were examined in relation to fasting and post-glucose insulin sensitivity. Adipocyte size, TG fatty acid composition and mRNA expression of lipogenic genes were determined.
  
  
  RESULTS
  We found strong positive relationships between adipose tissue TG content of the fatty acids myristic acid (14:0) and stearic acid (18:0) with insulin sensitivity (HOMA model) (p < 0.01 for each), and inverse relationships with adipocyte size (p < 0.01, p < 0.05, respectively). Variation in 18:0 content was the determinant of the adipose tissue TG 18:1 n-9/18:0 ratio, which correlated negatively with insulin sensitivity (p < 0.01), as observed previously. Adipose tissue 18:0 content correlated positively with the mRNA expression of lipogenic genes (e.g. FASN, p < 0.01). Lipogenic gene expression (a composite measure derived from principal components analysis) was inversely correlated with adipocyte cell size (p < 0.001). There was no relationship between dietary saturated fatty acid intake and adipose tissue 18:0 content.
  
  
  CONCLUSIONS
  Our data suggest a physiological mechanism whereby DNL is downregulated as adipocytes expand. Taken together with other data, they also suggest that hepatic and adipose tissue DNL are not regulated in parallel. We also confirm a strong relationship between small adipocytes and insulin sensitivity, which is independent of BMI.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Hodson
authors.forename: A L
authors.initials: AL
authors.lastname: Dennis
authors.forename: M J
authors.initials: MJ
authors.lastname: Neville
authors.forename: S M
authors.initials: SM
authors.lastname: Humphreys
authors.forename: K E
authors.initials: KE
authors.lastname: Harnden
authors.forename: K J
authors.initials: KJ
authors.lastname: Micklem
authors.forename: K N
authors.initials: KN
authors.lastname: Frayn
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis*; D008928:Mitochondria / Q000378:metabolism; D019814:Myristic Acid / Q000378:metabolism; D009765:Obesity / Q000150:complications; D019308:Palmitic Acid / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013229:Stearic Acids / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D012333:RNA, Messenger; D013229:Stearic Acids; D014280:Triglycerides; D019814:Myristic Acid; D019308:Palmitic Acid; C031183:stearic acid