Reduced bone marrow adrenergic receptor signaling is protective against weight gain and high fat‐induced hypertension

Abstract

INTRODUCTIONNeurogenic hypertension (HTN) is characterized by activation of immune system (IS) in part via elevated sympathetic nerve activity (SNA) to the bone marrow (BM). We have previously shown that chronic increase in BM SNA is linked with heightened release of inflammatory cells (ICs) in rodent models of HTN. Conversely, specific genetic ablation of BM beta adrenergic receptors results in a decrease in circulating ICs and reduces blood pressure (BP). Considering the role of both elevated SNA and IS in obesity, we hypothesized that reduction of SNA effects on BM ICs will dampen the inflammation and BP responses to high fat diet.METHODSBM mouse chimera was created by reconstituting sub‐lethally irradiated male C57BL/6J mice (6 weeks old) with whole BM cells isolated from either the adrenergic beta 1 and beta 2 receptor knock out (Adrb1.b2KO) mice (Jax Labs stock#003810), to generate BM C57‐Adrb1.b2 KO chimera, or the wild type C57BL/6J mice, to generate BM C57‐C57 control chimera. Success of reconstitution was confirmed by PCR for beta 1 and 2 adrenergic receptors in circulating cells following a 3 month recovery. Mice were placed on either control (10 kcal fat) or high fat diet (60 kcal fat) ad libitum for two weeks. Weight and food intake were measured twice weekly in all mice. BP measurements were taken using tail cuff at baseline, and thereafter three times a week throughout the study. Visceral fat pads were collected and weighed at the conclusion of the study. Flow cytometry was used to quantify circulating ICs (T cells, neutrophils, macrophages) and endothelial progenitor cells at endpoint.RESULTSBoth the BM C57‐C57 control chimera and BM C57‐Adrb1.b2 KO chimera mice had a statistically significant increase in total body weight following two weeks of high fat diet (by 5.33 g on average; P<0.05 vs control). However, only BM C57‐C57 control chimera mice had a significant increase in perirenal, epidymul, and retroperitoneal fat following high fat diet feeding (P<0.05). While mice on control diet had comparable BP values between the two groups, we observed a significantly elevated BP in BM C57‐C57 control chimera mice compared to the BM C57‐Adrb1.b2 KO chimera on high fat diet (mean systolic BP: 126.0 mmHg vs 105.7mmHg; p<0.05). However, no significant changes were observed in quantity of circulating CD4 T‐cells, macrophages, neutrophils or endothelial progenitors between the two mouse groups.CONCLUSIONReduced responsiveness of the BM hematopoietic cells to SNA is protective against high fat diet‐induced visceral fat gain and HTN, without significant changes in overall weight gain or circulating inflammatory cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.