Buspirone Induces Weight Loss and Normalization of Blood Pressure via the Stimulation of PPARδ Dependent Energy Producing Pathway in Spontaneously Hypertensive Rats.

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL PPAR Research Pub Date : 2023-01-01 DOI:10.1155/2023/7550164
Yong-Jik Lee, Hyun-Min Kim, Yoo-Na Jang, Yoon-Mi Han, Hong Seog Seo, Tae Woo Jung, Ji Hoon Jeong, Hyun Jung Lee, Kyung Oh Jung
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Abstract

Introduction: Buspirone, as a partial agonist for a 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), has been prescribed as an anxiolytic drug for patients. In addition, the lowering effect of serotonin on blood pressure was reported in hypertensive animal model. We investigated the therapeutic mechanism of buspirone against lipid metabolism disturbed by hypertension of early stage via hypertensive and obese animal model.

Methods: The levels of various biomarkers related to lipid metabolism and hypertension were estimated through the measurement of body weight and fat weight, blood analysis, western blotting, immunohistochemistry, and staining methods.

Results: The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 μM compared with untreated differentiated control. Body weight and abdominal fat weight were lowered in spontaneously hypertensive rats (SHRs) administered with buspirone of 10 mg/kg/day for 4 weeks than 8-week untreated group. Triglyceride (TG) level was decreased in SHRs administered with buspirone of 5 and 10 mg/kg/day compared to 8-week untreated group. High-density lipoprotein (HDL)-cholesterol concentration was elevated by buspirone 10 mg/kg/day treatment compared to 8-week untreated group. Blood pressures in SHRs were lowered by buspirone treatments of 5 and 10 mg/kg/day compared with 8-week untreated group. Protein levels for peroxisome proliferator-activated receptor δ (PPARδ), 5' adenosine monophosphate-activated protein kinase (AMPK), and PPARγ coactivator-1 alpha (PGC-1α) were increased both in C2C12 cells treated by buspirone of 100 μM and in SHRs administered by buspirone of 1, 5, and 10 mg/kg/day compared to untreated control cells and 8-week untreated group. Fat cell numbers decreased in 8-week untreated group were increased in SHRs administered by buspirone treats of 1, 5, and 10 mg/kg/day. Protein expression levels for angiotensin II type 1 receptor (AT1R) and vascular cell adhesion molecule 1 (VCAM1) were increased in 8-week untreated group compared to 4-week group, however, they were decreased by buspirone treatments of 1, 5, and 10 mg/kg/day.

Conclusion: Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPARδ dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.

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丁螺环酮通过刺激自发性高血压大鼠PPARδ依赖的能量产生途径诱导体重减轻和血压正常化。
丁螺环酮作为5-羟色胺(5-羟色胺)受体1A (5-HT1A)的部分激动剂,已被作为一种抗焦虑药物开给患者。此外,在高血压动物模型中报道了血清素对血压的降低作用。通过高血压和肥胖动物模型,探讨丁螺环酮对早期高血压引起的脂质代谢紊乱的治疗机制。方法:通过测量体重和脂肪量、血液分析、免疫印迹、免疫组织化学和染色等方法,评估与脂质代谢和高血压相关的各种生物标志物水平。结果:丁螺环酮浓度为50 μM和100 μM的3T3-L1细胞与未处理的分化对照组相比,脂质积累明显减少。丁螺环酮10 mg/kg/d给药4周后自发性高血压大鼠体重和腹部脂肪重量较未给药8周组明显降低。与8周未治疗组相比,给予丁螺环酮5和10 mg/kg/天的SHRs甘油三酯(TG)水平降低。与未治疗8周组相比,丁螺环酮10 mg/kg/d组高密度脂蛋白(HDL)-胆固醇浓度升高。与8周未治疗组相比,丁螺环酮治疗5和10 mg/kg/天可降低SHRs患者的血压。100 μM丁螺环酮处理的C2C12细胞和1、5、10 mg/kg/d丁螺环酮处理的SHRs细胞中,过氧化物酶体增殖体活化受体δ (PPARδ)、5′腺苷单磷酸活化蛋白激酶(AMPK)和PPARγ共激活因子-1α (PGC-1α)的蛋白水平均高于未处理的对照组和未处理8周的组。给予丁螺环酮1、5和10 mg/kg/天治疗的SHRs, 8周未治疗组脂肪细胞数量减少,脂肪细胞数量增加。与4周组相比,8周治疗组血管紧张素II型1受体(AT1R)和血管细胞粘附分子1 (VCAM1)的蛋白表达水平升高,而1、5和10 mg/kg/d丁螺环酮治疗组的蛋白表达水平降低。结论:丁螺环酮可能通过激活PPARδ依赖的分解代谢产生能量,导致体重和腹部脂肪重量的减少,最终改善脂质代谢,使高血压正常。
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来源期刊
PPAR Research
PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.20
自引率
3.40%
发文量
17
审稿时长
12 months
期刊介绍: PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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