Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity

Abstract

S-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation. Furthermore, hypothalamic levels of pro-inflammatory markers decrease, meanwhile those of the anti-inflammatory cytokine IL-10 increases. Interestingly, peripheral NEFA decreases alike circulating leptin and resistin levels. These data demonstrate that hypothalamic s-resistin controls fuel mobilization and adipokines secretion. Importantly, central s-resistin downregulation improves systemic insulin sensitivity, as demonstrated after an IPGTT. Interestingly, our data also indicate that s-resistin downregulation could improve hypothalamic inflammation in aged Wistar rats. Altogether, our findings suggest that hypothalamic s-resistin seems to be a key regulator of the brain-fat axis which links inflammation with metabolic homeostasis.

Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice

“…Resistin was found to cause insulin resistance 14 , 15 , 16 , 17 . It can completely reverse insulin resistance by normalizing plasma resistin level.…”

“…It can completely reverse insulin resistance by normalizing plasma resistin level. Subsequently, a large number of studies show that resistin plays an important role in the occurrence and development of a variety of inflammatory diseases 15 , 16 . It has been suggested that resistin may be a molecular link between inflammation, metabolism, and vascular dysfunction 18 , leading to the risk of MetS, type 2 diabetes, and cardiovascular disease.…”

The Role of Adipokines in the Control of Pituitary Functions

“…The destruction of the neurons of the arcuate nucleus significantly diminishes the expression of resistin in the pituitary gland [65]. In the hypothalamus, a shorter form of resistin (s-resistin), which is the intracellular form and is not secreted, was found [67]. The inhibition of s-resistin synthesis resulted in an increase in the activity of leptin signalling pathways and an insulin pathway in the rat hypothalamus.…”