The cAMP-phosphodiesterase PDE4B2 controls peroxisome proliferator-activated receptor γ expression and the initiation of adipogenesis in 3T3-L1 cells

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The cyclic adenosine monophosphate (cAMP)-phosphodiesterase 4 (PDE4) family comprises four genes that together are expressed as ∼25 protein variants. Nonselective PAN-PDE4 inhibition exerts various metabolic benefits, including reduced body weight and adiposity in humans and animals, but the role of individual PDE4s in mediating these effects remains ill-defined. We noticed that the hormonal induction of adipogenesis in 3T3-L1 preadipocytes increased the mRNA and protein expression of a single PDE4 variant, PDE4B2. Conversely, its siRNA-mediated knockdown markedly suppressed adipogenic differentiation and lipid accumulation, suggesting a critical role for PDE4B2 in adipogenesis. The onset of adipogenesis is well understood and involves the consecutive upregulation of proadipogenic transcription factors CCAAT-enhancer-binding proteins (C/EBPs) C/EBPδ, C/EBPβ, and C/EBPα, which ultimately induce peroxisome proliferator-activated receptor γ (PPARγ) as the master regulator of adipogenesis. PDE4B knockdown potently suppressed the upregulation of C/EBPα and PPARγ expression, thereby curbing the early steps in adipogenic differentiation. Mirroring its antiadipogenic effects in 3T3-L1 cells, PDE4B ablation in mice produces a lean phenotype characterized by reduced adipose tissue weight and reduced expression of C/EBPα and PPARγ. Although PPARγ agonists promote weight gain, they are als

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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