MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases

J Physiol Biochem. 2017 May;73(2):307-314. doi: 10.1007/s13105-016-0543-z. Epub 2016 Dec 14.

Abstract

Despite decades of research, obesity and diabetes remain major health problems in the USA and worldwide. Among the many complications associated with diabetes is an increased risk of cardiovascular diseases, including myocardial infarction and heart failure. Recently, microRNAs have emerged as important players in heart disease and energy regulation. However, little work has investigated the role of microRNAs in cardiac energy regulation. Both human and animal studies have reported a significant increase in circulating free fatty acids and triacylglycerol, increased cardiac reliance on fatty acid oxidation, and subsequent decrease in glucose oxidation which all contributes to insulin resistance and lipotoxicity seen in obesity and diabetes. Importantly, MED13 was initially identified as a negative regulator of lipid accumulation in Drosophilia. Various metabolic genes were downregulated in MED13 transgenic heart, including sterol regulatory element-binding protein. Moreover, miR-33 and miR-122 have recently revealed as key regulators of lipid metabolism. In this review, we will focus on the role of microRNAs in regulation of cardiac and total body energy metabolism. We will also discuss the pharmacological and non-pharmacological interventions that target microRNAs for the treatment of obesity and diabetes.

Keywords: Diabetes; Fatty acid oxidation; Lipid metabolism; MED13; MicroRNAs; Obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / therapeutic use
  • Cardiotonic Agents / therapeutic use
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism*
  • Drug Design
  • Energy Metabolism / drug effects
  • Gene Expression Regulation / drug effects
  • Heart Diseases / drug therapy
  • Heart Diseases / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Lipid Metabolism / drug effects
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Models, Biological*
  • Molecular Targeted Therapy
  • Obesity / drug therapy
  • Obesity / metabolism*

Substances

  • Anti-Obesity Agents
  • Cardiotonic Agents
  • Hypoglycemic Agents
  • MIRN122 microRNA, human
  • MIRN208 microRNA, human
  • MIRN33a microRNA, human
  • MicroRNAs