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A Designer Diet Induces Thermogenic Adipocytes via Raptor and Prolongs Healthy Lifespan

89 Pages Posted: 11 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Maurizio Ragni

Maurizio Ragni

University of Milan - Center for Study and Research on Obesity

Chiara Ruocco

University of Milan - Center for Study and Research on Obesity

Fabio Rossi

University of Milan - Center for Study and Research on Obesity

Pierluigi Carullo

Humanitas University

Veronica Ghini

Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine

Fabiana Piscitelli

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Adele Cutignano

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Emiliano Manzo

University of Geneva - Department of Cell Physiology and Metabolism

Rafael Maciel Ioris

University of Geneva - Department of Cell Physiology and Metabolism; University of Geneva, Faculty of Medicine, Diabetes Center

Franck Bontems

University of Geneva - Department of Cell Physiology and Metabolism

Laura Tedesco

University of Milan - Center for Study and Research on Obesity

Carolina Greco

Humanitas University

Annachiara Pino

University of Verona - Department of Diagnostics and Public Health

Ilenia Severi

Università Politecnica delle Marche - Department of Experimental and Clinical Medicine

Dianxin Liu

anderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Ryan P. Ceddia

Vanderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Luisa Ponzoni

University of Milan - Center for Study and Research on Obesity; Fondazione Umberto Veronesi

Leonardo Tenori

FiorGen Foundation; University of Florence - Center of Magnetic Resonance

Lisa Rizzetto

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

Matthias U. Scholz

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

Kieran Tuohy

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

Francesco Bifari

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity; University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Laboratory of Cell Metabolism and Regenerative Medicine

Vincenzo Di Marzo

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Claudio Luchinat

Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine; University of Florence - Department of Experimental and Clinical Medicine

Michele O. Carruba

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity

Saverio Cinti

Università Politecnica delle Marche - Department of Experimental and Clinical Medicine

Ilaria Decimo

University of Verona - Department of Diagnostics and Public Health

Gianluigi Condorelli

Humanitas University

Roberto Coppari

University of Geneva - Department of Cell Physiology and Metabolism; University of Geneva, Faculty of Medicine, Diabetes Center

Sheila Collins

Vanderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Alessandra Valerio

University of Brescia - Department of Molecular and Translational Medicine

Enzo Nisoli

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity

More...

Abstract

Reduced activity of thermogenic adipocytes leads to increased adiposity and defects in glucose metabolism. Thus, exploring dietary and molecular mechanisms able to stimulate these adipocytes is of paramount medical importance, as such mechanisms can be leveraged as a therapy for obesity and/or type 2 diabetes. Here, we show that a designer diet enriched in soluble essential amino acids can i) promote brown fat thermogenesis, ii) promote uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white adipose tissue, iii) prevent and reverse obesity and dysregulated glucose metabolism, and iv) prolong healthy lifespan in mice. Mechanistically, our data reveal that this nutritional approach induces mTOR complex 1 (mTORC1), and that the regulatory mTORC1-associated protein Raptor in adipocytes is required for the diet-induced beneficial effects. Hence, we identified a dietary regimen able to induce UCP1-dependent and -independent activation of thermogenic adipocytes, demonstrating a putative therapeutic approach for treating obesity and type 2 diabetes.

Keywords: Beige adipocytes, branched-chain amino acids, brown adipose tissue, lifespan, mitochondrial biogenesis, N-acyl amino acids, obesity, thermogenesis, type 2 diabetes, uncoupling protein 1.

Suggested Citation

Ragni, Maurizio and Ruocco, Chiara and Rossi, Fabio and Carullo, Pierluigi and Ghini, Veronica and Piscitelli, Fabiana and Cutignano, Adele and Manzo, Emiliano and Ioris, Rafael Maciel and Bontems, Franck and Tedesco, Laura and Greco, Carolina and Pino, Annachiara and Severi, Ilenia and Liu, Dianxin and Ceddia, Ryan P. and Ponzoni, Luisa and Tenori, Leonardo and Rizzetto, Lisa and Scholz, Matthias U. and Tuohy, Kieran and Bifari, Francesco and Di Marzo, Vincenzo and Luchinat, Claudio and Carruba, Michele O. and Cinti, Saverio and Decimo, Ilaria and Condorelli, Gianluigi and Coppari, Roberto and Collins, Sheila and Valerio, Alessandra and Nisoli, Enzo, A Designer Diet Induces Thermogenic Adipocytes via Raptor and Prolongs Healthy Lifespan (August 10, 2019). CELL-METABOLISM-D-19-00876. Available at SSRN: https://ssrn.com/abstract=3435269 or http://dx.doi.org/10.2139/ssrn.3435269
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Maurizio Ragni

University of Milan - Center for Study and Research on Obesity

Milan
Italy

Chiara Ruocco

University of Milan - Center for Study and Research on Obesity

Milan
Italy

Fabio Rossi

University of Milan - Center for Study and Research on Obesity

Milan
Italy

Pierluigi Carullo

Humanitas University

Via Rita Levi Montalcini, 4
Milan, 20090
Italy

Veronica Ghini

Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine

Italy

Fabiana Piscitelli

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Pozzuoli
Italy

Adele Cutignano

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Pozzuoli
Italy

Emiliano Manzo

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

Rafael Maciel Ioris

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

University of Geneva, Faculty of Medicine, Diabetes Center

Geneva
Switzerland

Franck Bontems

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

Laura Tedesco

University of Milan - Center for Study and Research on Obesity

Milan
Italy

Carolina Greco

Humanitas University

Via Rita Levi Montalcini, 4
Milan, 20090
Italy

Annachiara Pino

University of Verona - Department of Diagnostics and Public Health

Verona
Italy

Ilenia Severi

Università Politecnica delle Marche - Department of Experimental and Clinical Medicine

Ancona
Italy

Dianxin Liu

anderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Nashville, TN
United States

Ryan P. Ceddia

Vanderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Nashville, TN
United States

Luisa Ponzoni

University of Milan - Center for Study and Research on Obesity

Milan
Italy

Fondazione Umberto Veronesi

Milan
Italy

Leonardo Tenori

FiorGen Foundation

Sesto Fiorentino
Italy

University of Florence - Center of Magnetic Resonance

Sesto Fiorentino
Italy

Lisa Rizzetto

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

San Michele all'Adige
Italy

Matthias U. Scholz

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

San Michele all'Adige
Italy

Kieran Tuohy

Fondazione Edmund Mach - Department of Food Quality and Nutrition, Research and Innovation Center

San Michele all'Adige
Italy

Francesco Bifari

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity

Milan
Italy

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Laboratory of Cell Metabolism and Regenerative Medicine

Milan
Italy

Vincenzo Di Marzo

Italian National Research Council (CNR) - Institute of Biomolecular Chemistry

Pozzuoli
Italy

Claudio Luchinat

Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine

Italy

University of Florence - Department of Experimental and Clinical Medicine

Florence
Italy

Michele O. Carruba

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity

Milan
Italy

Saverio Cinti

Università Politecnica delle Marche - Department of Experimental and Clinical Medicine

Ancona
Italy

Ilaria Decimo

University of Verona - Department of Diagnostics and Public Health

Verona
Italy

Gianluigi Condorelli

Humanitas University

Via Rita Levi Montalcini, 4
Milan, 20090
Italy

Roberto Coppari

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

University of Geneva, Faculty of Medicine, Diabetes Center

Geneva
Switzerland

Sheila Collins

Vanderbilt University, School of Medicine, Department of Medicine, Division of Cardiovascular Medicine

Nashville, TN
United States

Alessandra Valerio

University of Brescia - Department of Molecular and Translational Medicine

Brescia
Italy

Enzo Nisoli (Contact Author)

University of Milan, Faculty of Medicine, Department of Medical Biotechnology and Translational Medicine, Center for Study and Research on Obesity ( email )

Milan
Italy

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