Fatty acids uptake and oxidation are increased in the liver of rats with adjuvant-induced arthritis

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1865; no. 3; pp. 696 - 707
• Main Authors: Wendt, Mariana M.N., de Oliveira, Monique Cristine, Franco-Salla, Gabriela B., Castro, Lorena Santos, Parizotto, Ângela V., Souza Silva, Francielli M., Natali, Maria R.M., Bersani-Amado, Ciomar A., Bracht, Adelar, Comar, Jurandir F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019
• Subjects: Adjuvant-induced arthritis; Fatty acids catabolism; Liver metabolism; Perfused rat liver; Rheumatoid cachexia; FFA; NFkB; MDH; Fatty acids catabolism; HDL; LDL; VLDL; LBM; MCT1; IL-1 and 6; CAT I and II; GSH; Liver metabolism; Perfused rat liver; HPLC; GSSG; ACC; Adjuvant-induced arthritis; Rheumatoid cachexia; PGC-1α; (FAT)/CD36; CS; TG; TNF-α; CoA; ROS; FAS; FA
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2018.12.019

Severe rheumatoid cachexia is associated with pronounced loss of muscle and fat mass in patients with advanced rheumatoid arthritis. This condition is associated with dyslipidemia and predisposition to cardiovascular diseases. Circulating levels of triglycerides (TG) and free fatty acids (FFA) have not yet been consistently defined in severe arthritis. Similarly, the metabolism of these lipids in the arthritic liver has not yet been clarified. Aiming at filling these gaps this study presents a characterization of the circulating lipid profile and of the fatty acids uptake and metabolism in perfused livers of rats with adjuvant-induced arthritis. The levels of TG and total cholesterol were reduced in both serum (10–20%) and liver (20–35%) of arthritic rats. The levels of circulating FFA were 40% higher in arthritic rats, possibly in consequence of cytokine-induced adipose tissue lipolysis. Hepatic uptake and oxidation of palmitic and oleic acids was higher in arthritic livers. The phenomenon results possibly from a more oxidized state of the arthritic liver. Indeed, NADPH/NADP+ and NADH/NAD+ ratios were 30% lower in arthritic livers, which additionally presented higher activities of the citric acid cycle driven by both endogenous and exogenous FFA. The lower levels of circulating and hepatic TG possibly are caused by an increased oxidation associated to a reduced synthesis of fatty acids in arthritic livers. These results reveal that the lipid hepatic metabolism in arthritic rats presents a strong catabolic tendency, a condition that should contribute to the marked cachexia described for arthritic rats and possibly for the severe rheumatoid arthritis. [Display omitted] •Lipolysis and serum levels of free fatty acids are increased in arthritic rats.•The fatty acids uptake and oxidation are increased in the perfused arthritic livers.•The hepatic overall NADH/NAD+ and NADPH/NADP+ ratios are reduced in arthritic rats.•It shifts the lipid metabolism toward a catabolic state in the arthritic liver.•Such a condition contributes to the marked cachexia verified in arthritic rats.