Butyric Acid Suppresses Adipogenesis Triggered by Intermittent Hypoxia and Hypercapnia via sAC/cAMP/PKA Pathway Modulation

Abstract Purpose: To explore whether intermittent hypoxia and hypercapnia i.e, intermittent hypoxic-hypercapnia (IHH), the main characteristics of obstructive sleep apnea (OSA), induce adipogenesis, and assess the inhibitory effect of butyric acid, (BA) on intermittent hypoxia or hypercapnia accelerated adipogenesis. Method: To determine the potential impact IHH on adipogenesis, cells were exposed to simultaneous transient hypoxic-hypercapnia (4% O₂, 10% CO₂) for 48 hours. Intracellular lipid and triglyceride accumulation of groups above was observed using an Oil Red O stain and triglyceride assay. To clarify the underlying mechanism, the expression level of the pro-adipogenic markers including peroxisome proliferator–activated receptor (PPAR)γ, CCAAT/enhancer binding protein (CEBP)α, CEBPβ and cAMP Response Element-Binding Protein (CREB) were measured. And the protein expression of soluble adenylyl cyclase (sAC) cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) was also assessed. Results: IHH accelerated lipid accumulation, triglyceride formation, and protein expression of PPARγ, CEBPα, CEBPβ and CREB which were inhibited by butyric acid. Additionally, butyric acid suppressed the sAC/cAMP/PKA pathway protein expression in IHH-induced adipogenesis. Conclusions: This study reveals that OSA-induced adipogenesis results from the synergistic effort of hypoxia and hypercapnia, also butyric acid could inhibit adipogenesis induced by hypoxic-hypercapnia via the suppression of sAC-dependent cAMP production and PKA activation.