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Diabetes Care Publish Ahead of Print published online ahead of print April 6, 2007
DOI: 10.2337/dc06-1962
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Original Research

The effect of beta-adrenergic and peroxisome proliferator-activated receptor gamma stimulation on target genes related to lipid metabolism in human subcutaneous adipose tissue

Iwona Bogacka, PhD1,,2, Thomas W. Gettys, PhD3, Lilian de Jonge, PhD4, Tuong Nguyen, BE4, Jana M. Smith, BS1, Hui Xie, MS1, Frank Greenway, MD1 and Steven R. Smith, MD1

1Molecular Endocrinology, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808
2Animal Physiology, Faculty of Biology, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland
3Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808
4Clinical Physiology, Pennington Biomedical Research Center, Baton Rouge, Louisiana, 70808

SmithSR{at}pbrc.edu

ABSTRACT

OBJECTIVE: The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. The study was undertaken to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in non-diabetic subjects.

RESEARCH DESIGN AND METHODS: Fifty seven women and men were randomized into groups: 1) placebo/placebo (PP); 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP); 3) placebo/pioglitazone (45 mg, PPio); 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression.

RESULTS: Body fat decreased by 6.0% in ECP and 4.6% in ECPio groups, whereas remained unchanged in the PPio or PP groups. Triglycerides levels decreased by -7.7, -24, -15.2, and -41mg/dL after 16 weeks treatment in the PP, PPio, ECP and ECPio groups respectively; indicating that pio with or without EC decreased triglycerides and EC with or without Pio decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl coenzyme A dehydrogenase and malonyl-CoA decarboxylase increased with PPio and ECPio. SteroylCoA desaturase decreased with ECP.

CONCLUSIONS: Combined activation of PPAR{gamma} and beta-adrenergic receptors has beneficial effects on body weight, plasma triglycerides and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism.

Clinical Trial Number: NCT00377975


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