Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

Abstract

Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported.

AMP-activated protein kinase activation suppresses leptin expression independently of adipogenesis in primary murine adipocytes

“…Adipogenesis requires convergence of many signalling pathways, all resulting in the initiation of transcription factor binding, followed by chromatin remodelling and, ultimately, adipogenic gene expression [ 8 , 24 ]. AMPK is known to interact with and/or modulate the expression of many of these factors, including ChrEBP, SREBP1-c/2, PPARγ and PGC1α, with documented AMPK-dependent repression of translocation, binding and/or expression in each case [ 42 , 48–54 ].…”

The Circulating Selenium Concentration Is Positively Related to the Lipid Accumulation Product: A Population-Based Cross-Sectional Study

“…Obesity is characterized by the growth of adipose cells and the enlargement of adipose tissue [8]. Body mass index (BMI) is a conventional, simple measurement that is applied to assess relative weight.…”

“…Selenium (Se), an essential trace element and constituent of selenoproteins, plays many vital physiological roles, including antioxidation, anti-inflammation, anti-aging, energy metabolism, immune regulation, redox signaling, cellular differentiation, protein folding, and gene expression [13][14][15][16][17][18][19][20][21][22]. Oxidative stress (OS), inflammation, endocrine function dysfunction, and energy metabolism disorders are key in the pathogenesis of obesity [8,[23][24][25].…”

Multimodal Strategies to Fight Obesity: Research on Tailored Therapies Based on Natural and Synthetic Compounds for Prevention, Management and Treatment

“…Beyond these emerging data, new insights for the development of therapeutic strategies against obesity come from the identification of epigenetic molecular targets. During adipogenesis, a highly orchestrated gene expression program occurs [ 47 ]. It favors the cell commitment of pluripotent stem cells (first stage) into pre-adipocytes, and then the terminal differentiation of pre-adipocytes into mature adipocytes (second stage) [ 48 ].…”

“…In recent years, such an aspect has been a hot topic in the scientific community, pushing the search for natural and synthetic compounds able to modulate that intricate network of proteins and transcription factors that are directly involved in stem cell differentiation or in uncontrolled adipocyte tissue hyperproliferation [ 50 , 51 ]. In this context, metformin and vitamin D have been revealed as very promising therapeutic agents, since their administration to adipose-derived stem cells upregulates HDAC1 expression, affected the stem cell phenotype and modulated the expression of those miRNAs playing a key role in stem cell adipogenesis [ 47 , 52 ].…”