Abstract
Triglyceride (TG) and its derivatives tend to be decreased in rheumatoid arthritis (RA) patients' blood when inflammation progresses. Aside from the role as a lipid buffer, white adipose tissue (WAT) contributes to this abnormality via adipokines, which regulate many metabolic signals. This work investigated adipokine-caused hepatic changes and their involvement in RA-related hypolipemia. Given their immune similarities with RA and pathological representativeness, adjuvant-induced arthritis (AIA) rats and antigen-induced arthritis (AA) mice were adopted. Adipokine levels in the liver were quantified, and their hepatic conditions were assessed by oxidative/enzymatic indicators. Besides kit-based metabolite quantification, fatty acid levels in blood were accurately determined by GC-MS. Metabolic differences between healthy and AIA rats were further characterized by UPLC-MS(2). In vitro, preadipocytes were stimulated by RA/AIA blood serum or together with rosiglitazone, a PPARγ agonist. The medium was used to culture HepG2 cells. Some AIA rats were subjected to adipectomy or rosiglitazone therapies. Being WAT-released mediators, IL-1β, IL-6, MCP-1, adiponectin, and visfatin were apparently increased in AIA/AA rodent models' liver, causing oxidative stress escalation, liver injuries, and fatty acid oxidation acceleration. This metabolic change was coincided to expression increase of CD36, FABP1, ATGL, and CPT-1A. PPARγ deficiency occurred both in vivo and in vitro under rheumatic conditions. RA serum reduced PPARγ expression and impaired its inhibition on NF-κB transcription activity in preadipocytes, which then led to excessive secretion of inflammatory adipokines. The corresponding medium down-regulated PPARγ and promoted expression of lipid catabolic enzymes in HepG2 cells. These effects were abrogated by rosiglitazone. Both the therapies impeded inflammatory secretion of WAT and fat catabolism of the liver. These data demonstrate that RA potentiates the capacity of WAT to secrete inflammatory adipokines. The resulting condition represses PPARγ expression and disrupts TG anabolism/catabolism balance in the liver. Because hepatocytes utilize more lipids but synthesize less, hypolipemia develops.