Reed Dominique, Kumar Dileep, Kumar Sushil, Raina Komal, Punia Reenu, Kant Rama, Saba Laura, Cruickshank-Quinn Charmion, Tabakoff Boris, Reisdorph Nichole, Edwards Michael G, Wempe Michael, Agarwal Chapla, Agarwal Rajesh
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Division of Critical Care Medicine and Cardiovascular Pulmonary Research, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Tradit Complement Med. 2021 Aug 19;12(3):287-301. doi: 10.1016/j.jtcme.2021.08.011. eCollection 2022 May.
Metabolic syndrome (MetS) is a complex disease of physiological imbalances interrelated to abnormal metabolic conditions, such as abdominal obesity, type II diabetes, dyslipidemia and hypertension. In the present pilot study, we investigated the nutraceutical bitter melon ( L) -intake induced transcriptome and metabolome changes and the converging metabolic signaling networks underpinning its inhibitory effects against MetS-associated risk factors.
Metabolic effects of lyophilized bitter melon juice (BMJ) extract (oral gavage 200 mg/kg/body weight-daily for 40 days) intake were evaluated in diet-induced obese C57BL/6J male mice [fed-high fat diet (HFD), 60 kcal% fat]. Changes in serum levels of biochemical parameters, gene expression in the hepatic transcriptome (microarray analysis using Affymetrix Mouse Exon 1.0 ST arrays), and metabolite abundance levels in lipid-phase plasma [liquid chromatography mass spectrometry (LC-MS)-based metabolomics] after BMJ intervention were assessed.
BMJ-mediated changes showed a positive trend towards enhanced glucose homeostasis, vitamin D metabolism and suppression of glycerophospholipid metabolism. In the liver, nuclear peroxisome proliferator-activated receptor (PPAR) and circadian rhythm signaling, as well as bile acid biosynthesis and glycogen metabolism targets were modulated by BMJ (p < 0.05). Thus, our in-depth transcriptomics and metabolomics analysis suggests that BMJ-intake lowers susceptibility to the onset of high-fat diet associated MetS risk factors partly through modulation of PPAR signaling and its downstream targets in circadian rhythm processes to prevent excessive lipogenesis, maintain glucose homeostasis and modify immune responses signaling.
代谢综合征(MetS)是一种与异常代谢状况相关的生理失衡复杂疾病,如腹型肥胖、II型糖尿病、血脂异常和高血压。在本初步研究中,我们调查了营养保健品苦瓜摄入引起的转录组和代谢组变化,以及支撑其对代谢综合征相关风险因素抑制作用的汇聚代谢信号网络。
在饮食诱导肥胖的C57BL/6J雄性小鼠[喂食高脂肪饮食(HFD),脂肪含量60千卡%]中评估冻干苦瓜汁(BMJ)提取物(每天经口灌胃200毫克/千克体重,持续40天)摄入的代谢效应。评估BMJ干预后血清生化参数水平的变化、肝脏转录组中的基因表达(使用Affymetrix Mouse Exon 1.0 ST阵列进行微阵列分析)以及脂质相血浆中的代谢物丰度水平[基于液相色谱质谱(LC-MS)的代谢组学]。
BMJ介导的变化呈现出增强葡萄糖稳态、维生素D代谢以及抑制甘油磷脂代谢的积极趋势。在肝脏中,BMJ调节了核过氧化物酶体增殖物激活受体(PPAR)和昼夜节律信号,以及胆汁酸生物合成和糖原代谢靶点(p < 0.05)。因此,我们的深度转录组学和代谢组学分析表明,摄入BMJ可部分通过调节PPAR信号及其在昼夜节律过程中的下游靶点,降低对高脂肪饮食相关代谢综合征风险因素发病的易感性,以防止过度脂肪生成、维持葡萄糖稳态并改变免疫反应信号。