Combined effects of MSU crystals injection and high fat-diet feeding on the establishment of a gout model in C57BL/6 mice

Abstract

Objective Gout is characterized by inflammatory arthritis with hyperuricaemia and deposition of monosodium urate (MSU) crystals in the joints. Several animal models have been proposed based on MSU crystals injection or high-fat diet feeding; however, neither hyperuricaemia model nor acute gout model can effectively reflect clinical features of gout. This study aimed to assess the effectiveness of a compound gout model induced by the combination of MSU crystals injection and high-fat diet feeding. Methods The compound gout model was induced by high-fat diet feeding per day and the intraplantar injection of MSU crystals (1 mg) into the footpad of each mouse every 10 days. Serum uric acid, foot swelling and pain analyses were performed at days 22, 32 and 42. Gout inflammation, serum proinflammatory cytokines and gut microbiota analyses were performed only at day 42. Results Compared to hyperuricaemia model or acute gout model, the compound gout model showed little advantages of elevating serum uric acid, causing foot swelling and gout inflammation, while it caused more severe serum inflammation and gut microbiota dysbiosis. Severe serum inflammation in the compound gout model could be reflected by the increased levels of IL-1α, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-γ, KC, MCP-1 and MIP-1β. In addition, the compound gout model induced more alterations in the gut microbiota, including increasing levels of Desulfovibrio and Parasutterella. Conclusion The injection of MSU and feed of high-fat diet have a combined effect on elevating serum inflammation and causing gut microbiota disorders in the process of establishing a gout model.

Effects of β-Carotin and Green Tea Powder Diets on Alleviating the Symptoms of Gouty Arthritis and Improving Gut Microbiota in C57BL/6 Mice

“…Studies have shown that the gut microbiota is involved in the response to MSU crystals in a gout model of mice, whereas the germ-free mice or mice treated with antibiotics do not respond to the injections of MSU crystals ( Vieira et al, 2015 ). Based on the 16S rRNA sequencing ( Lin et al, 2020b ), the top three relatively dominant phyla of the mouse gut microbiota were Firmicutes, Bacteroidetes, and Proteobacteria. In our study, the relatively dominant phyla of the mouse gut microbiota were Firmicutes and Bacteroidetes, while the MSU crystals and HFD altered the composition of the gut microbiota mainly by decreasing the relative abundance of Bacteroidetes.…”

“…Co., Ltd.) every day and were individually injected a total of 40 μl of phosphate buffered saline (PBS) into the right rear footpad once every 10 days. The other four groups of mice were fed daily with HFD (10% yeast extract) and were injected with MSU crystals (1 mg mixed in 40 μl PBS) into the right hind footpad once every 10 days ( Lin et al, 2020b ). The experiments lasted for 6 weeks after the mouse models of gouty arthritis were established.…”

“…A digital caliper (Meinaite, Germany) was used to measure the thickness of the footpads of each mouse before and 4, 24, 48, and 72 h after the injection of MSU crystals into the footpads of the mice. The degree of foot swelling in mice was calculated as the ratio of Δmm/mm (at zero time point) of the joints ( Lin et al, 2020b ). As described previously ( Chaplan et al, 1994 ), von Frey filaments (UGO Basile, Italy) were used to measure the mechanical retreat threshold (MWT) to estimate the foot pain threshold of mice.…”

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

“…given the strong association between this disease and obesity (31,32). This issue has been recently explored in a gout mouse model following footpad injections of MSU crystals in animals which were simultaneously fed with a high fat diet (containing 10% yeast extracts, likely to be an w-6 Fatty acid-rich diet, low in w-3 Fatty acids) (33). Interestingly, this model reproduced the rise in inflammatory cytokines seen in patients during acute gout flares, as well as the intestinal dysbiosis (commonly associated with high PUFA diet) which is also a hallmark of the disease (34).…”

Qu-Zhuo-Tong-Bi Decoction Alleviates Gouty Arthritis by Regulating Butyrate-Producing Bacteria in Mice

“…The control group was fed with a standard diet, and 40 μL of PBS was injected into the right hind footpad every 10 days. The animals in the other three groups were fed with HFD (10% yeast extract) and injected with MSU crystals (1 mg MSU crystals in 40 μL PBS/mouse) every 10 days to simulate gouty arthritis (Lin et al, 2020). Six-week therapy started at the induction of the gouty arthritis model.…”