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

Abstract

We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA) in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART) in the arcuate nucleus (ARC) does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats.

Appetite Regulation of TLR4-Induced Inflammatory Signaling

“…However, NPY mRNA expression in the hypothalamus increases in animal models of chronic inflammatory diseases characterized by cachexia, such as cancer cachexia and arthritis (51)(52)(53)(54)(55). However, this increase in NPY mRNA levels did not correlate with a decrease in food intake (52,54,56,57). It was associated with weight loss.…”

Hypothalamic inflammation and food intake regulation during chronic illness

“…Paradoxically, hypothalamic NPY gene expression is reported to be increased in animal models for chronic inflammatory diseases that are characterized by the presence of cachexia, such as cancer cachexia and arthritis [86][87][88][89][90][91]. However, this increase in mRNA levels did not correspond to the decrease in food intake [87,89,[91][92][93] (Fig. 1).…”

Cachexia – The Interplay Between the Immune System, Brain Control and Metabolism

“…In our study, food-restriction in arthritic rats led to a more profound decrease of mRNA expressions for anorexigenic factors (POMC, CART, IL-1 ) and marked increase of mRNA expressions for orexigenic factors (NPY, AgRP) in the ARC when compared to arthritic rats fed ad libitum . Moreover, food restriction in rats with adjuvant arthritis decreased arthritic score and parameters of inflammation including plasma leptin, but up-regulated plasma ghrelin and corticosterone levels (Jurcovicova et al, 2001;Stofkova et al, 2010). Accordingly, mild starvation through alterations in leptin and ghrelin levels may have protective antiinflammatory effects on signaling pathways in the hypothalamus that lead to conservation of body energy and favoring the foraging behavior.…”