Severity of Hypoxia-Induced Effects on 3T3-L1 Adipocyte Secretory Function Is Attenuated Dose-Dependently by Individual Short-Chain Fatty Acids

<b>Background</b>: Microbial fermentation of non-digestible carbohydrates and proteins produce short-chain fatty acids (SCFAs), which are critical communication signals in the gut-adipose tissue axis. Individual SCFA can differentially modulate the adipocyte secretory profile and adipose tissue metabolic function; however, their dose-dependent effects on adipocyte function in combined inflammatory and hypoxic environmental conditions that reflect the obesity-associated adipose tissue phenotype remain unknown. <b>Methods</b>: Mature 3T3-L1 adipocytes were cultured for 24 h with lipopolysaccharide (LPS; 10 ng/mL) plus 100 µM of cobalt chloride (CoCl₂) to chemically induce hypoxia ± individual SCFAs, namely acetate (Ace), propionate (Pro), and butyrate (But), in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM). <b>Results</b>: Ace, Pro and But reduced secretion of IL-6, MCP-1/CCL7 and Rantes/CCL5 in a dose-dependent manner, whereas Pro and But reduced MCP3/CCL7 secretion and only But reduced resistin and increased adiponectin secretion compared to control (<i>p</i> < 0.05). Intracellular protein expression of the ratio of phosphorylated-to-total NFκB p65 was reduced by 1 mM But, whereas the ratio of phosphorylated-to-total STAT3 expression was reduced by 1 mM Ace, Pro and But and 0.5 mM Pro and But compared to control (<i>p</i> < 0.05). There was no difference in insulin-stimulated or non-insulin-stimulated glucose uptake between control and any individual SCFAs (<i>p</i> > 0.05). <b>Conclusions</b>: Adipocyte adipokine secretory function in combined inflammation and hypoxic environmental conditions is dose-dependently attenuated by individual SCFA, which exhibit both individual and overlapping effects.