Differential influences of peroxisome proliferator-activated receptors gamma and -alpha on food intake and energy homeostasis.

Abstract

Chronic treatment with compounds activating peroxisome proliferator-activated receptor (PPAR)gamma and -alpha influences body energy stores, but the underlying mechanisms are only partially known. In a chronic-dosing study, equiefficacious antihyperglycemic doses of the PPAR gamma agonist pioglitazone and PPAR alpha/gamma dual activator ragaglitazar were administered to obesity-prone male rats. The PPAR alpha agonist fenofibrate had no effect on insulin sensitivity. Pioglitazone transiently increased and fenofibrate transiently decreased food intake, whereas ragaglitazar had no impact on feeding. As a result, body adiposity increased in pioglitazone-treated rats and decreased in fenofibrate-treated rats. PPAR gamma compounds markedly increased feed efficiency, whereas PPAR alpha agonist treatment decreased feed efficiency. In fenofibrate-treated rats, plasma acetoacetate was significantly elevated. Plasma levels of this potentially anorectic ketone body were unaffected in pioglitazone- and ragaglitazar-treated rats. High-fat feeding markedly increased visceral fat pads, and this was prevented by pioglitazone and ragaglitazar treatment. Pioglitazone treatment enlarged subcutaneous adiposity in high-fat-fed rats. In conclusion, PPAR gamma activation increases both food intake and feed efficiency, resulting in net accumulation of subcutaneous body fat. The impact of PPAR gamma activation on feeding and feed efficiency appears to be partially independent because the PPAR alpha component of ragaglitazar completely counteracts the orexigenic actions of PPAR gamma activation without marked impact on feed efficiency.

• Authors: Philip J Larsen, Per Bo Jensen, Rikke V Sørensen, Leif Kongskov Larsen, Niels Vrang, Erik M Wulff, Karsten Wassermann
• Journal: Diabetes (Diabetes) Vol. 52 Issue 9 Pg. 2249-59 (Sep 2003) ISSN: 0012-1797 [Print] United States
• PMID: 12941763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Hypolipidemic Agents
• Insulin
• Lipids
• Oxazines
• Phenylpropionates
• Receptors, Cytoplasmic and Nuclear
• Thiazoles
• Thiazolidinediones
• Transcription Factors
• ragaglitazar
• Fenofibrate
• Pioglitazone

Topics

• Adipose Tissue (physiology)
• Animals
• Biomarkers
• Blood Glucose
• Eating (drug effects, physiology)
• Energy Metabolism (drug effects, physiology)
• Fenofibrate (pharmacology)
• Gene Expression (drug effects, physiology)
• Glucose Tolerance Test
• Glycated Hemoglobin (analysis)
• Homeostasis (drug effects, physiology)
• Hypoglycemic Agents (pharmacology)
• Hypolipidemic Agents (pharmacology)
• Insulin (blood)
• Lipids (blood)
• Liver (physiology)
• Male
• Obesity (metabolism, physiopathology)
• Organ Size (physiology)
• Oxazines (pharmacology)
• Phenylpropionates (pharmacology)
• Pioglitazone
• Rats
• Rats, Mutant Strains
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Thiazoles (pharmacology)
• Thiazolidinediones
• Transcription Factors (metabolism)
• Weight Gain (physiology)