2. Academic Validation
  3. Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes

Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes

  • Stem Cell Reports. 2020 Apr 14;14(4):590-602. doi: 10.1016/j.stemcr.2020.03.002.
Max Friesen 1,  Curtis R Warren 2,  Haojie Yu 1,  Takafumi Toyohara 1,  Qiurong Ding 3,  Mary H C Florido 1,  Carolyn Sayre 1,  Benjamin D Pope 4,  Loyal A Goff 5,  John L Rinn 6,  Chad A Cowan 7
Affiliations

Affiliations

  • 1 Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
  • 2 Cardiometabolic Disease Research, Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
  • 3 CAS Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, P.R. China.
  • 4 Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  • 5 McKusick-Nathans Institute of Genomic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • 6 University of Colorado Boulder, Boulder, CO 80303, USA.
  • 7 Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. Electronic address: [email protected].
PMID: 32243843 DOI: 10.1016/j.stemcr.2020.03.002
Abstract

We previously discovered in mouse adipocytes an lncRNA (the homolog of human LINC00116) regulating adipogenesis that contains a highly conserved coding region. Here, we show human protein expression of a peptide within LINC00116, and demonstrate that this peptide modulates triglyceride clearance in human adipocytes by regulating lipolysis and mitochondrial β-oxidation. This gene has previously been identified as mitoregulin (MTLN). We conclude that MTLN has a regulatory role in adipocyte metabolism as demonstrated by systemic lipid phenotypes in knockout mice. We also assert its adipocyte-autonomous phenotypes in both isolated murine adipocytes as well as human stem cell-derived adipocytes. MTLN directly interacts with the β subunit of the mitochondrial trifunctional protein, an Enzyme critical in the β-oxidation of long-chain fatty acids. Our human and murine models contend that MTLN could be an avenue for further therapeutic research, albeit not without caveats, for example, by promoting white adipocyte triglyceride clearance in obese subjects.

Keywords

MTLN; adipocyte; human stem cells; metabolic disease; metabolism; mitochondrial metabolism.

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