Gene expression profiling of 3T3-L1 adipocytes exposed to phloretin.

Abstract

Adipocyte dysfunction plays a major role in the outcome of obesity, insulin resistance and related cardiovascular complications. Thus, considerable efforts are underway in the pharmaceutical industry to find molecules that target the now well-documented pleiotropic functions of adipocyte. We previously reported that the dietary flavonoid phloretin enhances 3T3-L1 adipocyte differentiation and adiponectin expression at least in part through PPAR gamma activation. The present study was designed to further characterize the molecular mechanisms underlying the phloretin-mediated effects on 3T3-L1 adipocytes using microarray technology. We show that phloretin positively regulates the expression of numerous genes involved in lipogenesis and triglyceride storage, including GLUT4, ACSL1, PEPCK1, lipin-1 and perilipin (more than twofold). The expression of several genes encoding adipokines, in addition to adiponectin and its receptor, is positively or negatively regulated in a way that suggests a possible reduction in systemic insulin resistance and obesity-associated inflammation. Improvement of insulin sensitivity is also suggested by the overexpression of genes associated with insulin signal transduction, such as CAP, PDK1 and Akt2. Many of these genes are PPAR gamma targets, confirming the involvement of PPAR gamma pathway in the phloretin effects on adipocytes. In light of these microarray data, it is reasonable to assume that phloretin may be beneficial for reducing insulin resistance, in a similar way to the thiazolidinedione class of antidiabetic drugs.

• Authors: Meryl Hassan, Claire El Yazidi, Christiane Malezet-Desmoulins, Marie-Josèphe Amiot, Alain Margotat
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 21 Issue 7 Pg. 645-52 (Jul 2010) ISSN: 1873-4847 [Electronic] United States
• PMID: 19576747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Adipokines
• PPAR gamma
• RNA, Messenger
• Phloretin

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, metabolism)
• Adipogenesis (drug effects)
• Adipokines (genetics, metabolism)
• Animals
• Carbohydrate Metabolism (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Mice
• Oligonucleotide Array Sequence Analysis
• PPAR gamma (physiology)
• Phloretin (pharmacology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)