Regulation of adipogenesis by medium-chain fatty acids in the absence of hormonal cocktail ☆ Jeong-Yeh Yang a , Mary Anne Della-Fera a,† , Srujana Rayalam a , Hea Jin Park a , Suresh Ambati a , Dorothy B. Hausman a , Diane L. Hartzell a , Clifton A. Baile a,b,† , ⁎ a Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602-2771, USA b Department of Foods and Nutrition, University of Georgia, Athens, GA 30602-2771, USA Received 14 February 2008; received in revised form 27 May 2008; accepted 28 May 2008 Abstract We report here that octanoate and decanoate, 8-carbon and 10-carbon medium-chain fatty acids (MCFA), decreased adipogenesis in 3T3-L1 preadipocytes when treated with standard hormonal cocktail, but increased adipogenesis in a dose-dependent manner (with decanoate being more effective) when treated with basal media. Addition of dexamethasone to basal medium with either octanoate or decanoate further increased adipogenesis. In order to understand the adipogenic effects of MCFA in the absence of standard hormonal cocktail, postconfluent 3T3-L1 preadipocytes were treated with octanoate or decanoate, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator- activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty-acid-binding protein, sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARγ and C/EBPα, with decanoate being more effective. Moreover, the PPARγ antagonist GW9662 inhibited MCFA-induced lipid accumulation by about 50%. Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARγ and other adipocyte-specific factors. © 2009 Elsevier Inc. All rights reserved. Keywords: MCFA; Adipocytes; Preadipocytes; Adipocyte-Specific Genes; GPDH activity 1. Introduction Obesity is characterized by an increase in lipid stores and is generally associated with enhanced lipid consump- tion, which contributes to its development [1]. Therefore, the study of the metabolic fate of dietary lipid in obese subjects is crucial in the understanding of this disease. Adipocyte differentiation is critical for metabolic home- ostasis and nutrient signaling. Growth of adipose tissue mass involves both hypertrophy and hyperplasia of adipocytes [2]. These processes result, respectively, from the increase in lipid accumulation in the adipocytes and the formation of new adipocytes from precursor cells, the preadipocytes. Preadipocytes differentiate into mature adipocytes when treated with a well-characterized inducing cocktail [3]. The sequence of events that leads to the expression of adipocyte-specific genes involves the activa- tion of several transcriptional factors, notably peroxisome- proliferator-activated receptor (PPAR) γ, CCAAT/enhan- cer-binding protein (C/EBP) α and sterol-regulatory element binding protein 1c (SREBP1c) [4]. PPARγ and C/EBPα control the expression of several adipocyte genes such as fatty-acid-binding protein (aP2) and fatty acid transporter (CD36). SREBP1c increases the expression of many lipogenic genes, including fatty acid synthase [5]. Available online at www.sciencedirect.com Journal of Nutritional Biochemistry 20 (2009) 537 – 543 ☆ This work was supported, in part, by grants from the Georgia Research Alliance and AptoTec, and by the Georgia Research Alliance Eminent Scholar endowment held by C.A. Baile. ⁎ Corresponding author. 444 Edgar L. Rhodes Center for Animal and Dairy Science, University of Georgia, Athens, GA 30602-2771, USA. Tel.: +1 706 542 2771; fax: +1 706 542 7925. E-mail address: cbaile@uga.edu (C.A. Baile). † Drs Baile and Della-Fera are investors in and serve on the Board of Directors for Apto Tec, Inc. 0955-2863/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2008.05.013