3 years ago

Male brown fat-specific double knockout of IGFIR/IR: Atrophy, mitochondrial fission failure, impaired thermogenesis and obesity.

C R Kahn, Manuel Benito, Gema García, Carlos Guillén, Silvia Fernández, Vanesa Viana-Huete, Ana García-Aguilar
It is unknown how the lack of IR (insulin receptor)/ IGFIR (insulin like growth factor receptor) in a tissue-specific manner does affect brown fat development and mitochondrial integrity and function and its impact on the redistribution of the adipose organ and the metabolic status. To address this important issue, we have developed the IR/IGFIR double knockout in brown adipose tissue-specific manner (DKO). Lack of those receptors caused a severe brown fat atrophy, an enhanced beige cell clusters in inguinal fat, loss of mitochondrial mass, mitochondrial damage related to cristae disruption, and the loss of proteins involved in autophagosome formation, mitophagy, mitochondrial quality control and dynamics and thermogenesis. More importantly, DKO mice showed an impaired thermogenesis upon cold exposure based on a failure in the mitochondrial fission mechanisms and a much lower UCP-1 (uncoupling protein 1) transcription rate and content. As a result, DKO under normal conditions showed an obesity susceptibility revealed by increased body fat mass and insulin resistance. Upon high fat diet, DKO mice displayed frank obesity as shown by increased body weight, increased adiposity, insulin resistance, hyperinsulinemia and hypertriglyceridemia, all consistent with a metabolic syndrome. Collectively, our data suggest a cause and effect relationship between a failure in the brown fat thermogenesis and an increased adiposity and obesity.

Publisher URL: http://doi.org/10.1210/en.2017-00738

DOI: 10.1210/en.2017-00738

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.