Adiponectin-Mediated Analgesia and AntiInflammatory Effects in Rat

The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation

Evaluating the effectiveness and underlying mechanisms of incretin-based treatments for hypothalamic obesity: A narrative review.

Hypothalamic obesity represents a clinical condition within the broader spectrum of obesity that frequently eludes detection and appropriate diagnosis. This subset of obesity is characterized by a dearth of established predictive markers and a paucity of standardized therapeutic protocols. The advent and rising prominence of glucagon-like peptide-1 (GLP-1) receptor agonists in the obesity treatment landscape present novel therapeutic avenues for hypothalamic obesity management. Nonetheless, critical inquiries persist concerning the efficacy of GLP-1 receptor (GLP-1R) agonists in this context, particularly regarding their central mechanisms of action and specific impact on hypothalamic obesity. In this narrative review, we concentrate on analyzing research papers that delineate the detection and function of GLP-1 receptors across various hypothalamic and cerebral regions. Additionally, we examine clinical research papers and reports detailing the application of GLP-1 receptor agonists in treating hypothalamic obesity. Furthermore, we include a concise presentation of a clinical case from our unit for contextual understanding. Currently, the clinical evidence supporting the efficacy of GLP-1 receptor agonists in hypothalamic obesity, as well as the diverse characteristics of this obesity subtype, remains insufficient. Preliminary data suggest that GLP-1R agonists might offer an effective treatment option, albeit with variable outcomes, particularly in younger patient cohorts. From a mechanistic perspective, the presence of GLP-1 receptors in various hypothalamic and broader brain regions potentially underpins the efficacy of GLP-1R agonists, even in instances of hypothalamic damage. Nevertheless, additional research is imperative to establish the functional relevance of these receptors in said brain regions. GLP-1R agonists represent a potential therapeutic option for patients with hypothalamic obesity. However, further clinical and basic/translational research is essential to validate the efficacy of these drugs across different presentations of hypothalamic obesity and to understand the functionality of GLP-1R in the diverse brain regions where they are expressed