Adipose tissue loss in adjuvant arthritis is associated with a decrease in lipogenesis, but not with an increase in lipolysis

Abstract

Adjuvant-induced arthritis is a model of rheumatoid arthritis that induces cachexia. In other cachectic situations, there is an increase in lipolysis resulting in a loss of adipose tissue mass. The aim of this work was to analyse the effect of chronic arthritis, induced by adjuvant injection, on white adipose tissue (WAT). For this purpose, rats were killed 10 days after adjuvant injection, when the first external symptoms appeared, on days 15 and 22 when the external signs of the illness reach their severest level. As arthritis decreases food intake, a pair-fed group was also included. Serum concentrations of insulin, leptin, adiponectin, glycerol and nitrites, as well as gene expression of leptin, adiponectin, hormonesensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor a and zinc-a 2 -glycoprotein (ZAG) were determined. Arthritis decreased food intake between days 5 and 16, but not during the last 5 days of the experiment. There was a marked decrease in relative adipose tissue weight and in serum leptin and adiponectin as well as in their gene expression in WAT in arthritic rats. Arthritis decreased the gene expression of FAS in the WAT. However, none of these effects was found in pair-fed rats. Arthritis did not increase lipolysis, since arthritic rats have lower serum concentrations of glycerol, HSL mRNA in WAT, as well as liver ZAG mRNA than the pair-fed or control rats. These data suggest that in chronic arthritis the decrease in white adipose mass is secondary to a reduced adipose lipogenesis, and this effect is not mainly due to the decrease in food intake.

Alterations in adipocyte glucose transporter GLUT4 and circulating adiponectin and visfatin in rat adjuvant induced arthritis

“…Our result on the reduction of circulating adiponectin levels during AA confirm the recent finding of Haruna et al (2007), Martin et al (2008), and our own observation (Stofkova et al 2009) in the clinical phase of AA, and suggests that this may be involved in the downregulation of GLUT4 in adipocytes. Any interpretation of reduced adiponectin plasma levels related to the severity of the disease can not be drawn, because the decisive role plays its intraarticular production.…”

Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors

“…Muscle wasting is associated with an increase in myostatin in cancer (10), whereas no modification in myostatin was observed in the skeletal muscle of arthritic rats. Furthermore, fat mass loss in arthritis is associated with a decrease in adipogenesis rather than an increase in lipolysis (31). On the other hand, in cancer, lipolysis is induced by an increase in zinc-␣ 2 -glycoprotein (ZAG), which plays an important role in loss of fat mass (4), whereas ZAG expression is not modified in arthritic rats (31).…”

“…Furthermore, fat mass loss in arthritis is associated with a decrease in adipogenesis rather than an increase in lipolysis (31). On the other hand, in cancer, lipolysis is induced by an increase in zinc-␣ 2 -glycoprotein (ZAG), which plays an important role in loss of fat mass (4), whereas ZAG expression is not modified in arthritic rats (31). In cancer cachexia, EPA Fig.…”

Emerging role of leptin in rheumatoid arthritis

“…Leptin comes mainly from adipose cells. Most studies have found significantly elevated serum levels of leptin in RA patients [7,18,22,[26][27][28]30,36,40,92,93], while others have found decreased levels [19,21,32,34]. Although the relationship is complex, leptin has been shown to be the major factor linkage of food intake with bone metabolism [94].…”