title: Geranylgeranyl pyrophosphate performs as an endogenous regulator of adipocyte function via suppressing the LXR pathway.
abstract: Isoprenoids such as geranylgeranyl pyrophosphate (GGPP) influence various biological processes. Here we show that GGPP inhibits adipocyte differentiation via the liver X receptors (LXRs) pathway. Intracellular GGPP levels and GGPP synthase (Ggps) mRNA expression increases during adipocyte differentiation. Ggps expression also increases in white adipose tissue of obese mice. GGPP addition reduces the expression of adipogenic marker genes such as adipocyte fatty acid binding protein, peroxisome proliferator-activated receptor γ, and insulin-stimulated glucose uptake. Similarly, over-expressing Ggps inhibits adipocyte differentiation. In contrast, Ggps knockdown promotes adipocyte differentiation. Inhibition of adipocyte differentiation by GGPP was partially reduced by LXR agonist T0901317. Furthermore, Ggps knockdown up-regulates LXR target genes during adipocyte differentiation. These results suggest that GGPP may act as an endogenous regulator of adipocyte differentiation and maturation through a mechanism partially dependent on the LXR pathway.
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Yu-Sheng
authors: YS
authors: Yeh
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan; Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan. Electronic address: tgoto@kais.kyoto-u.ac.jp.
authors: Tsuyoshi
authors: T
authors: Goto
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan; Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
authors: Nobuyuki
authors: N
authors: Takahashi
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Kahori
authors: K
authors: Egawa
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Haruya
authors: H
authors: Takahashi
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Huei-Fen
authors: HF
authors: Jheng
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors: Young-Il
authors: YI
authors: Kim
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan; Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
authors: Teruo
authors: T
authors: Kawada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D051231:Farnesyltranstransferase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D042541:Intracellular Space / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D015415:Biomarkers; C495428:Ggps1 protein, mouse; D000071518:Liver X Receptors; D009097:Multienzyme Complexes; D011106:Polyisoprenyl Phosphates; D051231:Farnesyltranstransferase; C002963:geranylgeranyl pyrophosphate
keywords: Adipocyte differentiation; Antagonist; GGPP; LXR; Metabolic syndrome