Authors: Katia Aquilano, Francesca Sciarretta, Riccardo Turchi, Bo Han Li, Marco Rosina, Veronica Ceci, Giulio Guidobaldi,Simona Arena, Chiara D’Ambrosio, Matteo Audano, Illari Salvatori, Barbara Colella, Raffaella Faraonio, Concita Panebianco, Valerio Pazienza, Donatella Caruso, Nico Mitro, Sabrina Di Bartolomeo, Andrea Scaloni, Jing-Ya Li, Daniele Lettieri-Barbato

Institutions:

  • Department Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome, Italy
  • Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
  • Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy
  • Department of Pharmacological and Biomolecular Sciences, University of MilanItaly
  • IRCCS Fondazione Santa Lucia, Rome, Italy
  • Department of Biosciences and Territory, University of Molise, Pesche (IS), Italy
  • Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
  • Gastroenterology Unit, Fondazione-IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG)Italy

Publication: Biorxiv

Date: February 2020

Full paper: https://www.biorxiv.org/content/10.1101/2020.02.26.966002v1

Abstract:

Low-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.