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In PDE3B KO mice, White Adipose Tissue (WAT) Exhibits Characteristics of “Good Fat”, i.e., Brown Adipose Tissue (BAT): I. Alterations in Mitochondrial Biogenesis and Function
Author(s) -
Chung Youn Wook,
Lagranha Claudia,
ZmudaTrzebiatowska Emilia,
Khan Faiyaz A,
Murphy Elizabeth
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.856.15
Subject(s) - white adipose tissue , mitochondrial biogenesis , mitochondrion , brown adipose tissue , adipose tissue , thermogenin , oxidative phosphorylation , microbiology and biotechnology , biology , beta oxidation , chemistry , medicine , adipose tissue macrophages , endocrinology , biochemistry , metabolism
To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of the Pde3b gene, which encodes Cyclic Nucleotide Phosphodiesterase 3B (PDE3B), an enzyme that catalyzes hydrolysis of cAMP and cGMP. In PDE3B‐KO mice, adipose tissue mass is reduced and epididymal white adipose tissue (EWAT) exhibits characteristics of BAT, including changes in morphology, and increased expression of genes related to BAT differentiation, mitochondrial biogenesis, and energy dissipation, including PPARγ coactivator‐1 alpha (PGC‐1α? and uncoupling protein 1 (UCP1). Mitochondria were isolated and studied by electron microscopic and proteomics techniques and functional assays. In KO EWAT, mitochondria are larger than WT mitochondria and uncoupled, with dysfunction of mitochondrial complex I, consuming less oxygen (using glutamate and malate as substrate) and generating less ATP than WT mitochondria. Proteomic patterns in KO mitochondria predict increased fatty acid β‐oxidation and decreased oxidative damage. In WAT to BAT differentiation, PDE3B is a critical molecular switch, inducing UCP1 to promote mitochondria uncoupling and inhibiting complex I to generate less oxidative stress. In KO mice, the presence of 'good fat' may compensate for hepatic insulin resistance.