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

## TL;DR

Short-chain fatty acids reduce inflammation in fat cells under stress conditions, with effects depending on the type and dose of fatty acid.

## Contribution

This study reveals how specific short-chain fatty acids dose-dependently reduce inflammation in hypoxic and inflamed fat cells.

## Key findings

- Acetate, propionate, and butyrate reduce secretion of pro-inflammatory cytokines like IL-6 and MCP-1 in a dose-dependent manner.
- Butyrate uniquely reduces resistin and increases adiponectin, while also lowering NFκB and STAT3 phosphorylation ratios.
- No significant effect of SCFAs on glucose uptake in adipocytes was observed.

## Abstract

Background: 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. Methods: 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). Results: 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 (p < 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 (p < 0.05). There was no difference in insulin-stimulated or non-insulin-stimulated glucose uptake between control and any individual SCFAs (p > 0.05). Conclusions: 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.