Glycogen synthase kinase 3β helps heart to pump better in obese patients.
Glycogen synthase kinase 3β helps heart to pump better in obese patients.
复制标题
糖原合成酶激酶 3β 有助于肥胖患者的心脏更好地泵血。
DOI：
10.1016/j.ijcard.2018.02.047
复制
发表时间：
2018
影响因子：
3.5
通讯作者：
Verma,SureshKumar
中科院分区：
文献类型：
--
作者：
Verma,SureshKumar
肥胖是一个日益严重的全球性问题，并与多种合并症相关，如2型糖尿病（T2 D）、类风湿性关节炎、认知障碍和痴呆、高血压、中风和心力衰竭[1]。全球肥胖症流行影响到所有年龄组。最近一项基于来自195个国家超过6800万受试者的体重指数（BMI）的研究表明，在过去20年中，全球高BMI受试者的代谢性疾病患病率增加[2]。BMI增加已被证明与几种疾病（包括心血管和中风相关疾病）有致病性关系[3]。在美国，心血管疾病（CVD）是最大的健康问题之一，超过三分之一的美国成年人患有至少一种形式的CVD [4]。众所周知，心力衰竭是肥胖和糖尿病等代谢性疾病患者死亡的主要原因。近年来，人们进行了许多研究，以开发更好的治疗肥胖患者心血管疾病的治疗策略，但成功率有限。Lal和他的小组在最新一期《国际心脏病学杂志》上的一项优雅的研究表明，心脏糖原合成酶激酶3β（GSK 3 β）在饮食诱导的肥胖模型中保留了心脏功能。糖原合成酶激酶3（GSK 3）是一种普遍表达的高度保守的丝氨酸/苏氨酸激酶，由Woodgett JR于1990年首次发现[5]。它主要参与几种调节蛋白的激素控制，包括糖原合成酶和转录因子c-jun [5]。GSK 3家族由两种亚型组成，即GSK 3 α和GSK 3 β。与大多数蛋白激酶不同，GSK-3在静息细胞中具有组成性活性，各种细胞刺激导致其磷酸化和抑制。考虑到与GSK 3相关的过程的范围，GSK 3已成为包括心血管疾病在内的各种疾病药物开发的重要靶点并不奇怪。在本期《国际心脏病学杂志》中，Gupte等人使用心脏特异性GSK 3 β条件性敲除小鼠，优雅地表明心肌细胞特异性GSK 3 β对肥胖小鼠的心脏功能至关重要，并且心肌细胞中的靶向GSK 3 β缺失加重了慢性高脂饮食诱导的肥胖GSK 3 β敲除（GSK 3 βKO）小鼠的心功能障碍。
Obesity is a growing problem worldwide and is associated with a wide range of comorbidities such as type-2 diabetes (T2D), rheumatoid arthritis, cognitive impairment and dementia, hypertension, stroke and heart failure [1]. The global obesity pandemic affects all age groups. A recent study, based on body mass index (BMI) in over 68 million subjects from 195 countries, suggests that prevalence of metabolic diseases was increased in high BMI subjects globally in the past 20 years [2]. The increased BMI has been shown to be pathogenically related to several diseases including cardiovascular and stroke-related diseases [3]. In the United States, cardiovascular diseases (CVD) are one of the greatest health issues, with greater than 1 in 3 American adults suffering from at least one form of CVD [4]. It is well established that the heart failure is the major cause of mortality in patients with metabolic diseases like obesity and diabetes. Recently, many investigations have been carried out to develop better therapeutic strategies for the treatment of cardiovascular diseases in obese patients with limited success. An elegant study by Lal and his group in the current issue of International Journal of Cardiology has shown that cardiac glycogen synthase kinase 3β (GSK3 β) preserves cardiac function in a diet-induced obesity model.Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed, highly conserved serine/threonine kinase, first identified by Woodgett JR in 1990 [5]. It is mainly involved in the hormonal control of several regulatory proteins including glycogen synthase and the transcription factor c-jun [5]. The GSK3 family consists of two isoforms viz. GSK3α and GSK3β. Unlike most protein kinases, GSK-3s are constitutively active in the resting cells and various cellular stimuli lead to their phosphorylation and inhibition. Given the range of processes associated with GSK3, it is not surprising that GSK3 has emerged as an important target for drug development in various diseases, including cardiovascular diseases. In this issue of International Journal of Cardiology, using cardiac-specific GSK3β conditional knockout mice, Gupte et al. elegantly showed that cardiomyocyte-specific GSK3β is critical for cardiac function in obese mice and targeted GSK3β deletion from cardiomyocyte exaggerated cardiac dysfunction in chronic high fat diet-induced obese GSK3β knockout (GSK3βKO) mice.