sodium-propionate and Disease-Models--Animal

Propionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.

Topics: Administration, Intravenous; Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Propionates; Rats; Rats, Sprague-Dawley; Stress, Psychological

Short-chain fatty acids (SCFAs) are the major products of the microbial fermentation of indigestible carbohydrates. SCFAs are known to improve the host metabolism, but their underlying mechanism of action remains elusive. In this study, 16 growing pigs were infused with saline or sodium propionate solution (25 mL, 2 mol/L) through a cecal fistula twice a day during a 28 day experimental period. The results showed that the cecal infusion of the SCFA propionate decreased serum and liver triglyceride levels and increased serum PYY secretion in growing pigs. Hepatic metabolomics identified 12 metabolites that were significantly altered by propionate. These included decreased levels of lipid metabolism-related stearic acid and glycerol-2-phosphate; increased levels of TCA cycle components including malic acid, fructose-6-phosphate, and succinic acid; and decreased levels of the amino acid metabolism products aspartic acid and serine. Hepatic transcriptomics demonstrated that propionate inhibited fatty acid synthesis and promoted the lipid metabolic process. Pathway enrichment analysis showed that propionate accelerated gluconeogenesis and decreased glycolysis. Taken together, these data support a role of the SCFA propionate on host lipid and glucose metabolism.

Topics: Animals; Cecum; Disease Models, Animal; Fistula; Glucose; Humans; Lipid Metabolism; Liver; Propionates; Swine; Transcriptome; Triglycerides