title: Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
abstract: We studied adipocytes from 8-week-old control rat offspring (CON) or rat offspring subjected to maternal low (8%) protein (MLP) feeding during pregnancy/lactation, a procedure predisposing to obesity. Acute exposure to isoproterenol or adenosine enhanced PDK4 and PPARγ mRNA gene expression in CON and MLP adipocytes. Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression. Higher levels of PDK4 and PPARγ were observed in MLP adipocytes. SCD1 is a PPARγ target. Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel. This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation. In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation. Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
authors: Centre for Diabetes, Blizard Institute, Barts and London School of Medicine and Dentistry, Queen Mary University of London, UK.
authors: Mark J
authors: MJ
authors: Holness
authors: Gulrez
authors: G
authors: Zariwala
authors: Celia G
authors: CG
authors: Walker
authors: Mary C
authors: MC
authors: Sugden
keywords: ADO, adenosine; Adipose tissue; BSA, bovine serum albumin; CON, control; HSL, hormone-sensitive lipase; ISO, isoproterenol; KRHB, Krebs–Ringer HEPES buffer; Lipogenesis; MLP, maternal low protein; NEFA, non-esterified fatty acid; PC, pyruvate carboxylase; PDC, pyruvate dehydrogenase complex; PDK, pyruvate dehydrogenase kinase; PEPCK, phosphoenolpyruvate carboxykinase; PPAR, peroxisome proliferator-activated receptor; Programming; Pyruvate dehydrogenase complex; SCD, stearoyl-CoA desaturase; TAG, triacylglycerol; WAT, white adipose tissue
references: Hum Reprod. 1997 Oct;12 Suppl 1:6-20
references: 9403317
references: Am J Physiol Cell Physiol. 2010 Nov;299(5):C1162-70
references: 20739620
references: Am J Physiol. 1999 Jan;276(1):E85-93
references: 9886954
references: Eur J Pharmacol. 2008 Nov 12;597(1-3):92-101
references: 18789919
references: J Endocrinol. 1999 Aug;162(2):313-9
references: 10425470
references: Diabetologia. 2010 Nov;53(11):2417-30
references: 20623219
references: Curr Opin Cell Biol. 1999 Dec;11(6):689-94
references: 10600710
references: Arch Physiol Biochem. 2006 Jul;112(3):139-49
references: 17132539
references: Physiol Behav. 2008 Apr 22;94(1):17-28
references: 18155097
references: J Clin Endocrinol Metab. 2008 Nov;93(11):4431-9
references: 18697866
references: FEBS Lett. 1982 Sep 20;146(2):327-30
references: 6128259
references: Int J Obes (Lond). 2007 Apr;31(4):723-9
references: 16953252
references: Proc Nutr Soc. 2009 Nov;68(4):370-7
references: 19698203
references: Essays Biochem. 2007;43:1-15
references: 17705789
references: J Biol Chem. 1964 Feb;239:375-80
references: 14169133
references: Diabetes. 1991 Dec;40 Suppl 2:115-20
references: 1748239
references: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4543-7
references: 15070754
references: Adv Pharmacol. 2011;61:145-86
references: 21586359
references: J Clin Invest. 2000 Sep;106(5):629-31
references: 10974014
references: Biochim Biophys Acta. 2011 Jan;1811(1):9-16
references: 20950707
references: Diabetes. 2008 Sep;57(9):2272-9
references: 18519799
references: Trends Endocrinol Metab. 2008 Dec;19(10):356-61
references: 18929494
references: Biochem J. 2001 Jul 1;357(Pt 1):183-93
references: 11415448