Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

Diabetologia. 2009 May;52(5):882-90. doi: 10.1007/s00125-009-1300-4. Epub 2009 Feb 28.

Abstract

Aims/hypothesis: 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/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipose Tissue / metabolism*
  • Biopsy
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Angiopathies / epidemiology
  • Fatty Acids / metabolism*
  • Fatty Acids, Nonesterified / blood
  • Gene Expression Regulation
  • Humans
  • Insulin Resistance
  • Lipids / biosynthesis*
  • Mitochondria / metabolism
  • Myristic Acid / metabolism
  • Obesity / complications
  • Palmitic Acid / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Reference Values
  • Stearic Acids / metabolism
  • Triglycerides / blood
  • Triglycerides / metabolism*

Substances

  • Blood Glucose
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Lipids
  • RNA, Messenger
  • Stearic Acids
  • Triglycerides
  • Myristic Acid
  • Palmitic Acid
  • stearic acid