Document Detail

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans.
MedLine Citation:
PMID:  19252892     Owner:  NLM     Status:  MEDLINE    
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.
R Roberts; L Hodson; A L Dennis; M J Neville; S M Humphreys; K E Harnden; K J Micklem; K N Frayn
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-28
Journal Detail:
Title:  Diabetologia     Volume:  52     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-06     Completed Date:  2009-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  882-90     Citation Subset:  IM    
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
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MeSH Terms
Adipocytes / cytology,  metabolism*
Adipose Tissue / metabolism*
Blood Glucose / metabolism
Diabetes Mellitus, Type 2 / complications,  epidemiology
Diabetic Angiopathies / epidemiology
Fatty Acids / metabolism*
Fatty Acids, Nonesterified / blood
Gene Expression Regulation
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,  metabolism*
Grant Support
BB/D008123/1//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids; 0/Fatty Acids, Nonesterified; 0/Lipids; 0/RNA, Messenger; 0/Stearic Acids; 0/Triglycerides; 544-63-8/Myristic Acid; 57-10-3/Palmitic Acid; 57-11-4/stearic acid

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