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Journal Article Ppublish 7 citations

PubMed: 38365172 DOI: 10.1016/j.jare.2024.02.001

The BET inhibitor JQ1 targets fat metabolism and counteracts obesity.

J Adv Res 68:403-413

Authors: Claudia Fornelli, Alessia Sofia Cento, Lorenzo Nevi, Raffaella Mastrocola, Gustavo Ferreira Alves, Giuseppina Caretti, Massimo Collino, Fabio Penna

Affiliations

  • Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
  • Department of Biosciences, University of Milano, Milan, Italy.
  • Department of Neurosciences "Rita Levi Montalcini", University of Torino, Turin, Italy.
  • Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.

Abstract

INTRODUCTION

Obesity, one of the most frequent health problems in the adult population, is a condition characterized by excessive white adipose tissue accumulation and accompanied by the increased risk to develop other disorders such as type II diabetes, cardiovascular disorders, physical disability, frailty and sarcopenia. Total fat mass frequently increases during aging, often coexisting with sarcopenia, thus resulting in an emerging condition defined sarcopenic obesity (SO). Our previous data demonstrated the relevant role of the bromo and extra-terminal domain (BET) proteins inhibitor JQ1 in attenuating inflammation and fibrosis in sarcopenic mice. Moreover, we preliminarily observed that JQ1 administration markedly reduces white adipose tissue mass, suggesting a potential role of BET proteins on visceral fat deposition during aging.

OBJECTIVES

Starting from those observations, the aim of this study was to investigate the ability of JQ1 to reduce adiposity in a chronic diet-induced obesity (DIO) mouse model mimicking the human metabolic syndrome.

METHODS

Male C57BL/6J mice were divided in subgroups, either fed a standard diet or a high fat diet for 22 or 12 weeks, treated over the last 14 days with JQ1 or with vehicle.

RESULTS

The results showed that JQ1 administration reduces fat mass, preserving skeletal muscle mass and function. A direct JQ1 lipolytic effect was demonstrated on mature adipocyte cultures. JQ1-mediated loss of adipose tissue mass was not associated with systemic inflammation or with lipid accumulation in muscle and liver. JQ1 administration did not impinge on skeletal muscle metabolism and oxidative capability, as shown by the lack of significant impact on mitochondrial mass and biogenesis.

CONCLUSION

In conclusion, the current data highlight a potential benefit of JQ1 administration to counteract obesity, suggesting epigenetic modulation as a prospective target in the treatment of obesity and sarcopenic obesity, despite the underlying multiorgan molecular mechanism is still not completely elucidated.

MeSH

Muscles, Aging, Diet, Obesity, Muscle, Skeletal, Tissues, Adipose Tissue, White, Adipose Tissue, Sarcopenia

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