Pharmacological Inhibition of PI3K Reduces Adiposity and Metabolic Syndrome in Obese Mice and Rhesus Monkeys

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2015 Mar 31

PMID 25817535

Citations 58

Authors

Ana Ortega-Molina

Elena Lopez-Guadamillas

Julie A Mattison

Sarah J Mitchell

Maribel Munoz-Martin

Gema Iglesias

Vincent M Gutierrez

Kelli L Vaughan

Mark D Szarowicz

Ismael Gonzalez-Garcia

Miguel Lopez

David Cebrian

Sonia Martinez

Joaquin Pastor

Rafael de Cabo

Manuel Serrano

Affiliations

Soon will be listed here.

Abstract

Genetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Long-term treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues. CNIO-PI3Ki treatment also ameliorates liver steatosis and decreases glucose serum levels. The above observations have been recapitulated in independent laboratories and using different oral formulations of CNIO-PI3Ki. Finally, daily oral treatment of obese rhesus monkeys for 3 months with low doses of CNIO-PI3Ki decreased their adiposity and lowered their serum glucose levels, in the absence of detectable toxicities. Therefore, pharmacological inhibition of PI3K is an effective and safe anti-obesity intervention that could reverse the negative effects of metabolic syndrome in humans.

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