Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging

Mol Cell Endocrinol. 2017 Nov 5:455:115-130. doi: 10.1016/j.mce.2016.12.022. Epub 2016 Dec 23.

Abstract

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.

Keywords: Age-related disease; Aging; Lipid metabolism; NAFLD; NASH.

Publication types

  • Review

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Aging / genetics
  • Aging / metabolism*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Glucose / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Leptin / genetics
  • Leptin / metabolism
  • Lipid Metabolism / genetics*
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Signal Transduction

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Insulin
  • Leptin
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Glucose