Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes

Shan Jiang, Han Chen, Zhigang Wang, Jean Jack Riethoven, Yuannan Xia, Jess Miner, Michael Fromm

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

trans-10, cis-12 Conjugated linoleic acid (t10. c12 CLA) reduces triglyceride levels in adipocytes. AMP-activated protein kinase (AMPK) and inflammation were recently demonstrated to be involved in the emerging pathways regulating this response. This study further investigated the role of AMPK and inflammation by testing the following hypotheses: (1) a moderate activation of AMPK and an inflammatory response are sufficient to reduce triglycerides, and (2) strong activation of AMPK is also sufficient. Experiments were performed by adding compounds that affect these pathways and by measuring their effects in 3T3-L1 adipocytes. A comparison of four AMPK activators (metformin, phenformin, TNF-α and t10. c12 CLA) found a correlation between AMPK activity and triglyceride reduction. This correlation appeared to be modulated by the level of cyclo-oxygenase (COX)-2 mRNA produced. Inhibitors of the prostaglandin (PG) biosynthetic pathway interfered with t10. c12 CLA's ability to reduce triglycerides. A combination of metformin and PGH2, or phenformin alone, efficiently reduced triglyceride levels in adipocytes. Microarray analysis indicated that the transcriptional responses to phenformin or t10. c12 CLA were very similar, suggesting similar pathways were activated. 3T3-L1 fibroblasts were found to weakly induce the integrated stress response (ISR) in response to phenformin or t10. c12 CLA and to respond robustly as they differentiated into adipocytes. This indicated that both chemicals required adipocytes at the same stage of differentiation to be competent for this response. These results support the above hypotheses and suggest compounds that moderately activate AMPK and increase PG levels or robustly activate AMPK in adipocytes may be beneficial for reducing adiposity.

Original languageEnglish (US)
Pages (from-to)656-664
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume22
Issue number7
DOIs
StatePublished - Jul 2011

Keywords

  • AMPK
  • Adipocyte
  • CLA
  • Metformin
  • Phenformin
  • Prostaglandin

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes'. Together they form a unique fingerprint.

  • Cite this