Gout and its relation to lipid metabolism. I. Serum uric acid, lipid, and lipoprotein levels in gout.

Blocking fatty acid–fueled mROS production within macrophages alleviates acute gouty inflammation

“…These treatments also suppressed macrophage-specific mROS production ( Figure 8, D and E). Given that flares of acute joint inflammation correlate with elevated serum FA levels (11,12), we examined the effects of elevated serum FAs on MSU crystal-driven, macrophage-specific mROS production through acute intravenous administration of intralipid (32). Coinjection of intralipid with the fluorescent FA analog BODIPY FL C 16 , which permits live imaging of FA transport within zebrafish larvae (33), into the circulation of Tg(kdrl:RFP) (34) larvae (possessing red fluorescent vasculature) revealed the immediate transport of injected lipids throughout the vasculature and progressive accumulation in the hindbrain ventricle within 1 hour ( Figure 9, A and B).…”

“…Previous studies have revealed that FAs can promote the proinflammatory phenotype of macrophages, in part through activation of NF-κB signaling (41). Furthermore, flares of acute joint inflammation in individuals with gout correlate with elevated serum FA levels (11,12), and the release of FAs into the circulation is a common metabolic consequence of a number of risk factors predisposing patients to flares (e.g., excessive alcohol and food consumption) (42). Of note, stearic acid has been shown to directly augment MSU crystal-stimulated IL-1β production by human PBMCs and murine macrophages through a TLR2/caspase 1-dependent mechanism (13).…”

“…One of these factors is fatty acids (FAs), which are a metabolic consequence of excessive alcohol and food consumption (risk factors for gout flares). Flares of acute joint inflammation in patients with gout correlate with elevated serum FA levels (11,12). In addition, FAs have been shown to augment MSU crystal-stimulated IL-1β secretion from human peripheral blood mononuclear cells (PBMCs) and murine macrophages (13).…”

The Diverse Roles of Phagocytes During Bacterial and Fungal Infections and Sterile Inflammation: Lessons From Zebrafish

“…The MSU crystals caused an immediate activation of tissue-resident macrophages and a subsequent inflammatory reaction, mimicking the acute gout flare in the joints of gout patients. The acute inflammatory reaction in the human condition is often connected to increased consumption of alcohol and purine-rich foods, which results in the substantial release of fatty acids (FAs) into the circulation (127). By live imaging metabolic processes [such as mitochondrial ROS (mROS) production; (128)] within macrophages during MSU-driven crystal inflammation, we were able to demonstrate that β-oxidation of FAs fueled macrophage activation through elevated mROS production (108).…”

Mechanism and treatment of hypertriglyceridaemia in gout.

“…Whether alcohol abuse is an additional cause which with obesity is sufficient to explain the phenomenon entirely remains controversial. Few studies have examined their independent contributions to hyperuricaemia and hypertriglyceridaemia simultaneously, and there is a common assumption that uric acid and triglyceride are linked by some alternative and fundamental metabolic mechanism (Mielants et al, 1973). In favour of this view is the reported concurrence of gout and elevated serum triglyceride levels in an isolated family (Bennett et al, 1973), the occasional reduction of serum triglyceride and enhanced triglyceride removal during allopurinol therapy (Bluestone et al, 1971), and the shared hypolipidaemic and uricosuric properties of both clofibrate (Trevaks and Lovell, 1965) and halofenate (Aronow et al, 1973).…”