Yamawaki Yosuke, Oue Kana, Shirawachi Satomi, Asano Satoshi, Harada Kae, Kanematsu Takashi
Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Department of Dental Anesthesiology, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Jpn Dent Sci Rev. 2017 Feb;53(1):18-24. doi: 10.1016/j.jdsr.2016.06.001. Epub 2016 Jun 27.
Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP), regulates lipolysis in white adipocytes and heat production in brown adipocytes phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.
肥胖被定义为异常或过度的脂肪堆积。脂肪中的慢性炎症会影响肥胖相关疾病的发展。许多报告指出,肥胖会增加多种疾病的发病风险,包括高血压、血脂异常、2型糖尿病、冠心病、中风、睡眠呼吸暂停以及乳腺癌、前列腺癌和结肠癌,从而导致死亡率上升。肥胖还与慢性神经病理状况如抑郁症和阿尔茨海默病有关。然而,有强有力的证据表明,体重减轻可通过限制血压并改善血清甘油三酯、总胆固醇、低密度脂蛋白(LDL)胆固醇和高密度脂蛋白(HDL)胆固醇水平来降低这些风险。肥胖的预防和控制很复杂,需要多方面的方法。阐明驱动脂肪代谢(脂肪生成和脂肪分解)的分子机制旨在开发控制肥胖的临床治疗方法。我们最近报道了一种脂肪代谢的新调节机制:一种蛋白磷酸酶结合蛋白,即磷脂酶C相关催化无活性蛋白(PRIP),可调节白色脂肪细胞中的脂肪分解以及棕色脂肪细胞中的产热——磷酸调节。小鼠中PRIP的缺乏导致脂肪堆积减少和能量消耗增加,从而产生瘦型表型。在此,我们评估PRIP作为控制肥胖的新治疗靶点。