Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

Thomas Obsen, Nils J. Faergeman, Soonkyu Chung, Kristina Martinez, Semone Gobern, Olivier Loreau, Martin Wabitsch, Susanne Mandrup, Michael McIntosh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [14C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [14C]-oleic or [14C]-linoleic acids. When using [14C]-acetic acid and [14C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA.

Original languageEnglish (US)
Pages (from-to)580-590
Number of pages11
JournalJournal of Nutritional Biochemistry
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Conjugated Linoleic Acids
Adipocytes
Lipids
Trans Fatty Acids
Stearoyl-CoA Desaturase
Isomers
Phospholipids
trans-10,cis-12-conjugated linoleic acid
Transcription Factors
Sterol Regulatory Element Binding Protein 1
Linoleic Acids
Glycerides
Monounsaturated Fatty Acids
Acyl Coenzyme A
Messenger RNA
Cardiolipins
Cholesterol Esters
Ceramides
Diglycerides
Adiposity

Keywords

  • Adipocytes
  • Conjugated linoleic acid
  • Lipid synthesis
  • Stearoyl-CoA desaturase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes. / Obsen, Thomas; Faergeman, Nils J.; Chung, Soonkyu; Martinez, Kristina; Gobern, Semone; Loreau, Olivier; Wabitsch, Martin; Mandrup, Susanne; McIntosh, Michael.

In: Journal of Nutritional Biochemistry, Vol. 23, No. 6, 01.06.2012, p. 580-590.

Research output: Contribution to journalArticle

Obsen, T, Faergeman, NJ, Chung, S, Martinez, K, Gobern, S, Loreau, O, Wabitsch, M, Mandrup, S & McIntosh, M 2012, 'Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes', Journal of Nutritional Biochemistry, vol. 23, no. 6, pp. 580-590. https://doi.org/10.1016/j.jnutbio.2011.02.014
Obsen, Thomas ; Faergeman, Nils J. ; Chung, Soonkyu ; Martinez, Kristina ; Gobern, Semone ; Loreau, Olivier ; Wabitsch, Martin ; Mandrup, Susanne ; McIntosh, Michael. / Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes. In: Journal of Nutritional Biochemistry. 2012 ; Vol. 23, No. 6. pp. 580-590.
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