Trans10, cis12 conjugated linoleic acid inhibits 3T3-L1 adipocyte adipogenesis by elevating β-catenin levels

Azadeh Yeganeh; Carla G Taylor; Jenna Poole; Leslee Tworek; Peter Zahradka

doi:10.1016/j.bbalip.2016.01.004

Trans10, cis12 conjugated linoleic acid inhibits 3T3-L1 adipocyte adipogenesis by elevating β-catenin levels

Biochim Biophys Acta. 2016 Apr;1861(4):363-70. doi: 10.1016/j.bbalip.2016.01.004. Epub 2016 Jan 9.

Authors

Azadeh Yeganeh¹, Carla G Taylor², Jenna Poole³, Leslee Tworek³, Peter Zahradka⁴

Affiliations

¹ Department of Physiology and Pathophysiology, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
² Department of Physiology and Pathophysiology, University of Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
³ Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
⁴ Department of Physiology and Pathophysiology, University of Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada. Electronic address: peterz@sbrc.ca.

PMID: 26780430
DOI: 10.1016/j.bbalip.2016.01.004

Abstract

Background: Trans-10, cis-12 (t10-c12) CLA treatment reduces lipid accumulation in differentiating mouse and human adipocytes, and decreases fat mass in mice, yet the mechanism of action remains unknown.

Objective: This study investigated the effect of the cis-9, trans-11 (c9-t11) and t10-c12 CLA isomers on the Wnt/β-catenin pathway, which has been reported to inhibit adipogenesis by down-regulating PPARγ.

Results: We observed that t10-c12 CLA treatment of 3T3-L1 adipocytes increases the levels of β-catenin and Ser-675 phosphorylated β-catenin due to inhibition of its degradation. These changes in β-catenin were not linked to either the Wnt/β-catenin agonist Wnt10b or other upstream effectors such as SFRP-5. Paradoxically, the presence of higher amounts of β-catenin did not elevate cyclin D1 levels, which is recognized as a critical target gene. Neither of the CLA isomers affected the localization of β-catenin in the cytosol and nucleus as determined by immunofluorescence microscopy. However, subcellular fractionation suggested the level of cytosolic β-catenin was reduced in t10-c12 CLA treated cells. Immunoprecipitation revealed that t10-c12 CLA increased the interaction of β-catenin and PPARγ.

Conclusions: t10-c12-CLA inhibits adipocyte differentiation by increasing β-catenin stability in 3T3-L1 adipocytes, thus enhancing sequestration of PPARγ in an inactive complex, which prevents progression of adipogenesis.

Keywords: Adipocytes; Adipogenesis; Conjugated linoleic acid (CLA); GSK3-β; PPARγ; Wnt; β-Catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3-L1 Cells
Adipocytes / drug effects*
Adipocytes / metabolism
Adipogenesis / drug effects*
Animals
Linoleic Acids, Conjugated / pharmacology*
Mice
PPAR gamma / metabolism
Phosphorylation
Protein Binding
Protein Stability
Time Factors
Up-Regulation
Wnt Signaling Pathway / drug effects
beta Catenin / metabolism*

Substances

CTNNB1 protein, mouse
Linoleic Acids, Conjugated
PPAR gamma
beta Catenin
trans-10,cis-12-conjugated linoleic acid