The Effect of β-Adrenergic and Peroxisome Proliferator–Activated Receptor-γ Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue

Abstract

OBJECTIVE -The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted 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 nondiabetic subjects. RESEARCH DESIGN AND METHODS-A total of 57 women and men were randomized into four 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), and 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 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by Ϫ7.7, Ϫ24, Ϫ15.2, and Ϫ41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP.CONCLUSIONS -Combined activation of peroxisome proliferator-activated receptor-␥ and ␤-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.

Determination and regulation of body composition in elite athletes

“…Although the mechanisms behind clenbuterol's anabolic action are not fully understood, it is known that it is largely through stimulation of β 2 adrenergic receptors. This leads to activation of adenylate cyclase with generation of cAMP and increased phosphorylation of enzymes resulting in increases in protein synthesis and reduced protein breakdown accompanied by increased lipolysis36 and upregulation of genes required for fatty acid catabolism 110. There is also a shift from slow oxidative to fast glycolytic muscle fibre type profile and changes in intracellular calcium metabolism 32 35 36.…”

Dietary activators of Sirt1

“…Sirt1 mRNA levels were shown to increase in adipose tissue with a sixteen-week treatment of a combination of ephedrine, caffeine and the anti-diabetic drug Pioglitazone in nondiabetic human subjects (Bogacka, et al 2007). …”

Sibutramine effect on metabolic control of obese patients with type 2 diabetes mellitus treated with pioglitazone

“…In fact, the insulin sensitivity improvement associated with the use of some antidiabetic drugs could lead to a further accumulation of adipose tissue [7], even if mainly located in the subcutaneous tissue and not in the more dangerous visceral one. This effect has been clearly demonstrated with efficacious insulin-sensitizing drugs acting on peroxisome proliferator-activated receptor-γ, such as thiazolidinediones [8].…”