Abstract
In the past several decades obesity has become one of the greatest health burdens worldwide. Diet high in fats and fructose is one of the main causes for the prevalence of metabolic disorders including obesity. Promoting brown or beige adipocyte development and activity is regarded as a potential treatment of obesity. Mondo family transcription factors including MondoA and carbohydrate response element binding protein (ChREBP) are critical for nutrient-sensing in multiple metabolic organs including the skeletal muscle, liver, adipose tissue and pancreas. Under normal nutrient conditions, MondoA and ChREBP contribute to maintaining metabolic homeostasis. When nutrient is overloaded, Mondo family transcription factors directly regulate glucose and lipid metabolism in brown and beige adipocytes or modulate the crosstalk between metabolic organs. In this review, we aim to provide an overview of recent advances in the understanding of MondoA and ChREBP in sensing nutrients and regulating obesity or related pathological conditions.
Highlights
The epidemic of obesity has emerged as a worldwide public health issue
MondoA limits glucose uptake and glycolysis mostly in skeletal muscle and immune cells, while ChREBP promotes de novo lipogenesis in liver and adipose tissue
In pathological states of nutrient overload, MondoA could interfere with insulin signaling, while adipose ChREBP is linked to systemic insulin sensitivity and its role extends from white to brown and beige adipose tissues
Summary
The epidemic of obesity has emerged as a worldwide public health issue. In 2017, the Global Burden of Disease Study estimated that high body mass index (BMI), one of the leading risk factors, accounted for 4.72 million deaths and 148 million disability-adjusted life-years (DALYs) [1]. The urgent need for weight-loss treatments has given rise to multiple attempts to target cellular metabolism and restore systemic energy homeostasis, among which is the strategy of promoting brown and beige adipocyte activity and development. Enhancing activities of brown and beige adipocytes promotes energy expenditure through heat generation, and enhances glucose metabolism and protects against insulin resistance [6,7,8,9,10,11], which provides promising therapeutic effects to counteract obesity and related diseases
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