Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenesis in subcutaneous adipose tissue
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
Affiliations
Katia Aquilano
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy; Corresponding author.
Francesca Sciarretta
IRCCS Fondazione Santa Lucia, Rome, Italy
Riccardo Turchi
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy
Bo-Han Li
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Marco Rosina
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy
Veronica Ceci
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy
Giulio Guidobaldi
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy
Simona Arena
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy
Chiara D'Ambrosio
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy
Matteo Audano
Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy
Illari Salvatori
IRCCS Fondazione Santa Lucia, Rome, Italy
Barbara Colella
Department of Biosciences and Territory, University of Molise, Pesche, IS, Italy
Raffaella Faraonio
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
Concita Panebianco
Gastroenterology Unit, Fondazione-IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo, FG, Italy
Valerio Pazienza
Gastroenterology Unit, Fondazione-IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo, FG, Italy
Donatella Caruso
Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy
Nico Mitro
Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy
Sabrina Di Bartolomeo
Department of Biosciences and Territory, University of Molise, Pesche, IS, Italy
Andrea Scaloni
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy
Jing-Ya Li
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Daniele Lettieri-Barbato
Department Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy; Corresponding author. Department Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome, Italy.
Low-protein/high-carbohydrate (LPHC) diet has been suggested to promote 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.
