Obesity under the moonlight of c-MYC

Abstract

The moonlighting protein c-Myc is a master regulator of multiple biological processes including cell proliferation, differentiation, angiogenesis, apoptosis and metabolism. It is constitutively and aberrantly expressed in more than 70% of human cancers. Overwhelming evidence suggests that c-Myc dysregulation is involved in several inflammatory, autoimmune, metabolic and other non-cancerous diseases. In this review, we addressed the role of c-Myc in obesity. Obesity is a systemic disease, accompanied by multi-organ dysfunction apart from white adipose tissue (WAT), such as the liver, the pancreas, and the intestine. c-Myc plays a big diversity of functions regulating cellular proliferation, the maturation of progenitor cells, fatty acids (FAs) metabolism, and extracellular matrix (ECM) remodeling. Moreover, c-Myc drives the expression of a wide range of metabolic genes, modulates the inflammatory response, induces insulin resistance (IR), and contributes to the regulation of intestinal dysbiosis. Altogether, c-Myc is an interesting diagnostic tool and/or therapeutic target in order to mitigate obesity and its consequences.

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

“…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.…”

“…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 ).…”

MYC: there is more to it than cancer

“…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 ).…”