RT Journal Article
SR Electronic
T1 Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.26.966002
DO 10.1101/2020.02.26.966002
A1 Katia Aquilano
A1 Francesca Sciarretta
A1 Riccardo Turchi
A1 Bo-Han Li
A1 Marco Rosina
A1 Veronica Ceci
A1 Giulio Guidobaldi
A1 Simona Arena
A1 Chiara D’Ambrosio
A1 Matteo Audano
A1 Illari Salvatori
A1 Barbara Colella
A1 Raffaella Faraonio
A1 Concita Panebianco
A1 Valerio Pazienza
A1 Donatella Caruso
A1 Nico Mitro
A1 Sabrina Di Bartolomeo
A1 Andrea Scaloni
A1 Jing-Ya Li
A1 Daniele Lettieri-Barbato
YR 2020
UL http://biorxiv.org/content/early/2020/02/27/2020.02.26.966002.abstract
AB 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.