Abstract

Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F, but not PGE2, is significantly increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF was dose-dependently decreased. These studies demonstrate that PGF was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF, either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF signaling with the PGF receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells.

Original languageEnglish (US)
Pages (from-to)30-37
Number of pages8
JournalProstaglandins and Other Lipid Mediators
Volume99
Issue number1-2
DOIs
StatePublished - Oct 1 2012

Fingerprint

Conjugated Linoleic Acids
Dinoprost
Adipocytes
Fatty Acids
Gene expression
Isomers
Gene Expression
Messenger RNA
Epiregulin
Prostaglandins F
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Mitogens
Epidermal Growth Factor Receptor
Dinoprostone
Weight Loss
Pharmacology
Ligands

All Science Journal Classification (ASJC) codes

  • Physiology
  • Biochemistry
  • Pharmacology
  • Cell Biology

Cite this

@article{b3803a7f4cc44e2a95cc1f5c8b55921c,
title = "The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2 dependent PGF2α synthesis in adipocytes",
abstract = "Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F2α, but not PGE2, is significantly increased 10 fold. In female BALB/c mice fed 0.5{\%} 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF2α was dose-dependently decreased. These studies demonstrate that PGF 2α was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF2α, either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF2α signaling with the PGF2α receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells.",
author = "Belda, {Benjamin J.} and Thompson, {Jerry T.} and Raghu Sinha and Prabhu, {Kumble Sandeep} and {Vanden Heuvel}, {John Patrick}",
year = "2012",
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TY - JOUR

T1 - The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2 dependent PGF2α synthesis in adipocytes

AU - Belda, Benjamin J.

AU - Thompson, Jerry T.

AU - Sinha, Raghu

AU - Prabhu, Kumble Sandeep

AU - Vanden Heuvel, John Patrick

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F2α, but not PGE2, is significantly increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF2α was dose-dependently decreased. These studies demonstrate that PGF 2α was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF2α, either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF2α signaling with the PGF2α receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells.

AB - Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F2α, but not PGE2, is significantly increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF2α was dose-dependently decreased. These studies demonstrate that PGF 2α was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF2α, either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF2α signaling with the PGF2α receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells.

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U2 - 10.1016/j.prostaglandins.2012.05.001

DO - 10.1016/j.prostaglandins.2012.05.001

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