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

Abstract

Abstract. Rheumatoid arthritis in humans brings about impaired insulin sensitivity and glucose tolerance. Since adipose tissue plays a role in glucose homeostasis, we evaluated the size of adipocytes, the amount of glucose transporter type 4 (GLUT4) in adipocyte plasma membranes, and circulating insulin, glucose, and adipokines affecting glucose metabolism, resistin, adiponectin and visfatin during experimental adjuvant arthritis (AA) in male Lewis rats. AA was induced by a single injection of complete Freund's adjuvans. Adipocyte diameter was assessed microscopically, GLUT4 was measured by Western blotting. Plasma insulin, adiponectin, visfatin were quantitated by RIA, and resistin by ELISA. Arthritic rats showed cachexia, reduced adipocyte size, and downregulated membrane GLUT4 (4065 ± 962 vs. 9911 ± 680 arb. units of optic density, p < 0.01), reduced plasma adiponectin (1.956 ± 0.10 vs. 3.16 ± 0.22 µg/ml, p < 0.001), and enhanced visfatin (1.84 ± 1.05 vs. 1.24 ± 0.1 ng/ml, p < 0.01). Plasma glucose and insulin were unaltered, as were the resistin levels. Conclusion: AA induced cachexia results in reduction of adipocyte size, and paradoxically also in downregulation of GLUT4 in adipocyte membranes. This is supposed to be functionally related to the reduced adiponectin levels. The upregulated visfatin in rat arthritis is a novel finding, and it confirms its role in autoimmunity across the species.

Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

“…Our study confirmed previous observations that AA under the condition of normofeeding decreased circulating levels of leptin [18, 22, 23], and adiponectin [19, 23, 24], and increased circulating levels of visfatin [25], ghrelin [19, 26], and corticosterone [7, 18, 19, 27]. Regarding the severity of arthritis, the most important finding of this investigation is the reduced arthrogram score associated with a profound decrease of circulating leptin and a marked increase of circulating ghrelin and corticosterone levels due to the food restriction.…”

“…Furthermore, in inflammatory arthritis, overweight considerably contributes to insulin resistance, while calorie restriction together with disease-modifying antirheumatic drugs result in its improvement [64]. Our previous results showed downregulation of glucose transporter GLUT4 in adipocyte membranes in arthritic rats that may indicate decreased insulin sensitivity in AA [25]. In this study we did not observe any significant changes in HOMA index, in normally fed or arthritic rats on high-fat diet.…”

Adipokines, Metabolic Syndrome and Rheumatic Diseases

“…In fact, it has been reported that serum and SF levels of visfatin were increased in arthritis models [128–130]. Clinical data also suggest a role for visfatin in the development of RA.…”

Adiponectin in inflammatory and immune-mediated diseases

“…These characteristics are likely associated with enhanced ability to produce APN. On the other hand, no change in adipocyte size but higher inflammation was reported in subcutaneous adipose tissue of COPD patients [116], while reduced adipocyte size in the presence of low, rather than high, APN is present in rats with adjuvant-induced arthritis [122]. These data suggest that the association between disease, adipocyte size and APN production is likely complex and needs to be investigated on a case-by-case basis.…”