Department of Pediatrics, University of Pittsburgh School of Medicine, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Mol Cell Endocrinol. 2017 Nov 5;455:115-130. doi: 10.1016/j.mce.2016.12.022. Epub 2016 Dec 23.
Aging is associated with dysregulation of glucose and lipid metabolism. Various factors that contribute to the dysregulation include both modifiable (e.g. obesity, insulin resistance) and non-modifiable risk factors (age-associated physiologic changes). Although there is no linear relationship between aging and prevalence of non-alcoholic fatty liver disease, current data strongly suggests that advanced age leads to more severe histological changes and poorer clinical outcomes. Hepatic lipid accumulation could lead to significant hepatic and systemic consequences including steatohepatitis, cirrhosis, impairment of systemic glucose metabolism and metabolic syndrome, thereby contributing to age-related diseases. Insulin, leptin and adiponectin are key regulators of the various physiologic processes that regulate hepatic lipid metabolism. Recent advances have expanded our understanding in this field, highlighting the role of novel mediators such as FGF 21, and mitochondria derived peptides. In this review, we will summarize the mediators of hepatic lipid metabolism and how they are altered in aging.
衰老与葡萄糖和脂质代谢失调有关。导致这种失调的各种因素包括可改变的(如肥胖、胰岛素抵抗)和不可改变的风险因素(与年龄相关的生理变化)。虽然衰老与非酒精性脂肪性肝病的患病率之间没有线性关系,但目前的数据强烈表明,高龄会导致更严重的组织学变化和更差的临床结局。肝脂质堆积可导致严重的肝和全身后果,包括脂肪性肝炎、肝硬化、全身葡萄糖代谢受损和代谢综合征,从而导致与年龄相关的疾病。胰岛素、瘦素和脂联素是调节肝脂质代谢的各种生理过程的关键调节剂。最近的进展扩展了我们在这一领域的认识,强调了新型介质如 FGF21 和线粒体衍生肽的作用。在这篇综述中,我们将总结肝脂质代谢的调节剂以及它们在衰老过程中的变化。