The Chemerin-CMKLR1 Axis is Functionally important for Central Regulation of Energy Homeostasis

• DOI: 10.3389/fphys.2022.897105
• Publication Date: 2022-06-01T07:31:16Z
• Authors: Haesung Yun; Rebecca Dumbell; Katie Hanna; Junior Bowen; Samantha L. McLean; Sriharsha Kantamneni; Klaus Pors; Qing-Feng Wu; Gisela Helfer
• Keywords: Chemerin; Energy homeostasis

Chemerin is an adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism, has been hypothesized as a link between obesity type II diabetes. In humans affected by obesity, chemerin gene expression peripheral tissues circulating levels are elevated. mice, plasma of upregulated high-fat feeding gain loss function studies show association with body weight, food intake glucose homeostasis. Therefore, important blood-borne mediator that, amongst its other functions, controls appetite weight. Almost all to date have focused on release from adipose tissue effects the central largely overlooked. To demonstrate role chemerin, we manipulated signaling hypothalamus, brain region associated regulation, using pharmacological genetic manipulation approaches. Firstly, selective receptor CMKLR1 antagonist α-NETA was administered i.c.v. rats test for acute physiological effect. Secondly, designed short-hairpin-RNA (shRNA) lentivirus construct targeting CMKLR1. This shRNA construct, or control injected bilaterally into arcuate nucleus male Sprague Dawley diet (45%). After surgery, were maintained 2 weeks then switched chow further weeks. We found significant weight acutely inhibition chronically. difference became apparent after switch nucleus-CMKLR1 knockdown rats. not accompanied blood levels. Interestingly, appetite-regulating neuropeptides remained unaltered, however, reduction inflammatory marker TNF-α suggesting reduced protects induced neuroinflammation. white brown tissue, mRNA receptors markers lipogenesis adipocyte activation unchanged confirming that driven brain. Our behavioral analyses suggest had impact object recognition. data functionally regulation