Autophagy and mitochondria in obesity and type 2 diabetes

Jaakko Sarparanta, Marina García-Macia, Rajat Singh

Research output: Contribution to journalReview articlepeer-review

74 Scopus citations

Abstract

Obesity and type 2 diabetes are growing health problems worldwide. The three principal diabetogenic factors are adiposity, insulin resistance in skeletal muscle, and decreased insulin production by pancreatic cells. During recent years, macroautophagy (hereafter autophagy) sequestration and lysosomal degradation of cellular components has emerged as an important player in these processes, playing a protective role against development of insulin resistance and diabetes. Of particular importance is the removal of dysfunctional mitochondria via mitophagy, a form of macroautophagy selective for mitochondria. Both muscle insulin resistance and β-cell dysfunction largely depend on metabolic overload of mitochondria, which results in incomplete β-oxidation, oxidative stress, accumulation of toxic lipid intermediates, and mitochondrial damage. Mitophagy eliminates this vicious cycle of oxidative stress and mitochondrial damage, and thus counteracts pathogenic processes. Autophagy also mediates exercise-induced increases in muscle glucose uptake and protects β cells against ER stress in diabetogenic conditions. On the other hand, adipose tissue autophagy promotes adipocyte differentiation, possibly through its role in mitochondrial clearance. Being involved in many aspects, autophagy appears to be an attractive target for therapeutic interventions against obesity and diabetes. Here we explore the connections of autophagy with mitochondria in obesity and type 2 diabetes, and discuss its roles in diabetic complications. Understanding how autophagy protects against diabetes could help design new strategies against this growing epidemic.

Original languageEnglish (US)
JournalCurrent Diabetes Reviews
Volume12
DOIs
StatePublished - 2016

Keywords

  • Adipose tissue
  • Beta cells
  • Diabetes
  • Macroautophagy
  • Mitophagy
  • Muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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