Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity

• Published in: Cell 2003-04, Vol.113 (2), p.159-170
• Main Authors: Wang, Yong-Xu, Lee, Chih-Hao, Tiep, Sambath, Yu, Ruth T, Ham, Jungyeob, Kang, Heonjoong, Evans, Ronald M
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adipose Tissue, Brown - metabolism; Animals; Body Weight - genetics; Dietary Fats - pharmacology; Energy Metabolism - genetics; Fatty Acids - metabolism; Food, Formulated; Genetic Vectors; Lipid Metabolism; Mice; Mice, Knockout; Mice, Transgenic; Obesity - genetics; Obesity - metabolism; Obesity - physiopathology; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Leptin; Recombinant Fusion Proteins; Thiazoles - pharmacology; Transcription Factors - agonists; Transcription Factors - drug effects; Transcription Factors - metabolism; Transgenes - genetics; Triglycerides - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(03)00269-1

In contrast to the well-established roles of PPARγ and PPARα in lipid metabolism, little is known for PPARδ in this process. We show here that targeted activation of PPARδ in adipose tissue specifically induces expression of genes required for fatty acid oxidation and energy dissipation, which in turn leads to improved lipid profiles and reduced adiposity. Importantly, these animals are completely resistant to both high-fat diet-induced and genetically predisposed ( Lepr db/db ) obesity. As predicted, acute treatment of Lepr db/db mice with a PPARδ agonist depletes lipid accumulation. In parallel, PPARδ-deficient mice challenged with high-fat diet show reduced energy uncoupling and are prone to obesity. In vitro, activation of PPARδ in adipocytes and skeletal muscle cells promotes fatty acid oxidation and utilization. Our findings suggest that PPARδ serves as a widespread regulator of fat burning and identify PPARδ as a potential target in treatment of obesity and its associated disorders.