Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats.
Fibrates are hypolipidemic drugs that activate the peroxisome proliferator-activated receptors. Since fibrates may also increase energy expenditure, we investigated whether fenofibrate (FF) had this effect in diet-induced obese rats. A 2-month administration of a high-fat palatable diet to adult rats increased body weight by 25% and white adipose mass by 163% compared with a standard diet. These effects were prevented by FF, both when administered for the 2 months of high-fat feeding and when given for only the second month. Consequently, FF-treated rats had a final body weight and white adipose tissue mass similar to untreated animals on the standard diet. FF also increased resting metabolic rate, hepatic peroxisomal and mitochondrial palmitoyl-dependent oxygen uptake and mRNA levels of acyl-CoA oxidase and lipoprotein lipase. Finally, FF lowered mRNA levels of uncoupling protein-2 and did not affect mitochondrial respiration in skeletal muscle. Therefore, FF seems to act as a weight-stabilizer mainly through its effect on liver metabolism.
Mancini
F P
FP
Facoltá di Scienze Matematiche, Fisiche e Naturali, Universitá del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
Lanni
A
A
Sabatino
L
L
Moreno
M
M
Giannino
A
A
Contaldo
F
F
Colantuoni
V
V
Goglia
F
F
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004032:Diet / Q000009:adverse effects; D004734:Energy Metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010101:Oxygen Consumption; D020675:Peroxisomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014475:Uncoupling Agents; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011345:Fenofibrate