Obesity under the moonlight of c-MYC

Nevzorova, Yulia A.; Cubero, Francisco Javier

doi:10.3389/fcell.2023.1293218

Cited by 3 publications

(3 citation statements)

References 152 publications

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“…Outside the domain of cancer, c-Myc plays a significant physiological and pathological role ( Rosselot et al, 2021 ; Nevzorova and Cubero, 2023 ; Prochownik and Wang, 2023 ; Zacarias-Fluck et al, 2024 ). Although therapeutic interventions involving direct c-Myc manipulation may present challenges, the protective effects observed across various parameters suggest that its targeting may offer an approach to mitigate obesity-associated complications.…”

Section: Discussionmentioning

confidence: 99%

“…The transcription factor c-Myc plays an important physiological role controlling multiple cellular functions ( Hofmann et al, 2015 ; Zacarias-Fluck et al, 2024 ). Deregulated c-Myc expression has been associated with cancer, metabolic and inflammatory conditions ( Zheng et al, 2017 ; Luo et al, 2021 ; Rosselot et al, 2021 ; Nevzorova and Cubero, 2023 ; Zacarias-Fluck et al, 2024 ). Several reports from our group and others have highlighted an essential role of the transcription factor c-Myc in endothelial cell function in development ( Baudino et al, 2002 ; He et al, 2008 ; Rodrigues et al, 2008 ; Kokai et al, 2009 ) and disease ( Riu et al, 2002 ; Riu et al, 2003 ; Hurley et al, 2010 ; Florea et al, 2013 ; Rosselot et al, 2019 ; Qi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity

Machi,

Altilio,

et al. 2024

Front. Cell Dev. Biol.

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Introduction: Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity. In the present work we report a novel endothelial-mediated mechanism essential for regulation of metabolic homeostasis, driven by c-Myc.Methods: We used conditional knockout (EC-Myc KO) and overexpression (EC-Myc OE) mouse models to investigate the endothelial-specific role of c-Myc in metabolic homeostasis during aging and high-fat diet exposure. Body weight and metabolic parameters were collected over time and tissue samples collected at endpoint for biochemical, pathology and RNA-sequencing analysis. Animals exposed to high-fat diet were also evaluated for cardiac dysfunction.Results: In the present study we demonstrate that EC-Myc KO triggers endothelial dysfunction, which precedes progressive increase in body weight during aging, under normal dietary conditions. At endpoint, EC-Myc KO animals showed significant increase in white adipose tissue mass relative to control littermates, which was associated with sex-specific changes in whole body metabolism and increase in systemic leptin. Overexpression of endothelial c-Myc attenuated diet-induced obesity and visceral fat accumulation and prevented the development of glucose intolerance and cardiac dysfunction. Transcriptome analysis of skeletal muscle suggests that the protective effects promoted by endothelial c-Myc overexpression are associated with the expression of genes known to increase weight loss, energy expenditure and glucose tolerance.Conclusion: Our results show a novel important role for endothelial c-Myc in regulating metabolic homeostasis and suggests its potential targeting in preventing obesity and associated complications such as diabetes type-2 and cardiovascular dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity

Machi,

Altilio,

et al. 2024

Front. Cell Dev. Biol.

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“…Overall, MYC plays multiple roles in obesity, including the maturation of progenitor cells, fatty acid metabolism and extracellular matrix remodelling. Of note, MYC modulates the inflammatory response, induces insulin resistance, and regulates intestinal dysbiosis ( Nevzorova and Cubero, 2023 ).…”

Section: Myc’s Involvement In Diseases and Conditionsmentioning

confidence: 99%

MYC: there is more to it than cancer

Zacarías-Fluck,

Soucek,

Whitfield

2024

Front. Cell Dev. Biol.

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MYC is a pleiotropic transcription factor involved in multiple cellular processes. While its mechanism of action and targets are not completely elucidated, it has a fundamental role in cellular proliferation, differentiation, metabolism, ribogenesis, and bone and vascular development. Over 4 decades of research and some 10,000 publications linking it to tumorigenesis (by searching PubMed for “MYC oncogene”) have led to MYC becoming a most-wanted target for the treatment of cancer, where many of MYC’s physiological functions become co-opted for tumour initiation and maintenance. In this context, an abundance of reviews describes strategies for potentially targeting MYC in the oncology field. However, its multiple roles in different aspects of cellular biology suggest that it may also play a role in many additional diseases, and other publications are indeed linking MYC to pathologies beyond cancer. Here, we review these physiological functions and the current literature linking MYC to non-oncological diseases. The intense efforts towards developing MYC inhibitors as a cancer therapy will potentially have huge implications for the treatment of other diseases. In addition, with a complementary approach, we discuss some diseases and conditions where MYC appears to play a protective role and hence its increased expression or activation could be therapeutic.

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Common Denominator of MASLD and Some Non-Communicable Diseases

Ferenc,

Jarmakiewicz-Czaja,

Sokal-Dembowska

et al. 2024

CIMB

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Currently, steatohepatitis has been designated as metabolic dysfunction-associated steatohepatitis (MASLD). MASLD risk factors mainly include metabolic disorders but can also include genetic, epigenetic, and environmental factors. Disease entities such as obesity, diabetes, cardiovascular disease, and MASLD share similar pathomechanisms and risk factors. Moreover, a bidirectional relationship is observed between the occurrence of certain chronic diseases and MASLD. These conditions represent a global public health problem that is responsible for poor quality of life and high mortality. It seems that paying holistic attention to these problems will not only help increase the chances of reducing the incidence of these diseases but also assist in the prevention, treatment, and support of patients.

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Obesity under the moonlight of c-MYC

Cited by 3 publications

References 152 publications

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity

Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity

MYC: there is more to it than cancer

Common Denominator of MASLD and Some Non-Communicable Diseases

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