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


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 -7.7, -24, -15.2, and -41 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-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.
Bogacka
Iwona
I
Molecular Endocrinology Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
Gettys
Thomas W
TW
de Jonge
Lilian
L
Nguyen
Tuong
T
Smith
Jana M
JM
Xie
Hui
H
Greenway
Frank
F
Smith
Steven R
SR
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002110:Caffeine / Q000494:pharmacology; D004809:Ephedrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008055:Lipids / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000187:drug effects / Q000502:physiology*; D000077205:Pioglitazone; D010919:Placebos; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012867:Skin / Q000033:anatomy & histology; D045162:Thiazolidinediones / Q000494:pharmacology
D008055:Lipids; D047495:PPAR gamma; D010919:Placebos; D011943:Receptors, Adrenergic, beta; D045162:Thiazolidinediones; D002110:Caffeine; D004809:Ephedrine; D000077205:Pioglitazone