**2. Redox state changes under obese condition and in the process of adipogenesis**

It is viewed that obesity is a state of chronic oxidative stress. In obese patients, increased oxidative metabolic products of DNA, protein and lipid, and/or decreased antioxidant activity are closely associated with excessive fat accumulation. In high fat (HF) diet-fed animals, oxidative stress precedes the onset of insulin resistance and obesity. In obese animals, levels of reactive oxygen species (ROS) in mature adipocytes are higher than that in other tissues, including liver, skeletal muscle, and aorta. In the course of adipogenesis, intracellular redox potentials tend to a significant oxidizing state. It is suggested that increased ROS level is associated with the development of obesity and may be required for the formation of new adipocytes.

#### **2.1. ROS and adipogenesis**

ROS plays a controversial role in adipogenesis. On the one hand, ROS is a required signal molecule in the activation of key transcription factors responsible for adipogenesis. On the other hand, ROS may also act as a negative regulator of the formation of adipocytes.

#### **2.2. ROS is a signal required for adipogenesis**

It is originally identified that ROS is produced physiologically during adipogenesis. In the last decades, accumulating data prove that endogenously generated ROS acts as an essential mediator for adipogenic differentiation. Compared with that of preadipocytes, adipocytes have a relatively higher rate of spontaneous intra- and extracellular ROS production. Adipogenic hormonal cocktails could increase ROS production in preaipocytes and enhance the process of differentiation. C/EBPβ and PPARγ are the main factors that mediate the proadipogenic effect of ROS.

#### **2.3. ROS also functions as a detrimental signal of adipogenesis**

It is shown that oxidative stress inhibits fat cell formation by reducing the C/EBP DNAbinding activity [5]. Mitochondrial ROS could inhibit preadipocyte proliferation, indicating that it can influence adipocyte differentiation through inhibiting MCE. In 3T3-F442A preadipocytes treated with various pharmacological inhibitors, Carriere et al. [6] demonstrated that mitochondrial ROS was negatively correlated with adipocyte differentiation through increasing adipogenic repressor CHOP-10/GADD153.

#### **2.4. ROS-producing systems and adipocyte differentiation**

mass may result from the enhancement of adipocyte formation (adipocyte differentiation, also called adipogenesis), enlargement of adipocyte (lipogenesis), and/or reduction of lipolysis that contribute to fat accumulation in WAT. Adipocyte differentiation is defined as the formation of new adipocytes from multipotent stem cells or preadipocyte precursors [3]. In brief, adipogenesis is divided into four steps, including initial growth arrest, mitotic clonal expansion (MCE), early differentiation, and terminal differentiation-development of mature adipocyte phenotype [4]. White and brown adipocyte differentiation share common pathways and possess specific characteristics. Unless specified, "adipocyte differentiation or adipogenesis"

**2. Redox state changes under obese condition and in the process of** 

of obesity and may be required for the formation of new adipocytes.

**2.3. ROS also functions as a detrimental signal of adipogenesis**

It is viewed that obesity is a state of chronic oxidative stress. In obese patients, increased oxidative metabolic products of DNA, protein and lipid, and/or decreased antioxidant activity are closely associated with excessive fat accumulation. In high fat (HF) diet-fed animals, oxidative stress precedes the onset of insulin resistance and obesity. In obese animals, levels of reactive oxygen species (ROS) in mature adipocytes are higher than that in other tissues, including liver, skeletal muscle, and aorta. In the course of adipogenesis, intracellular redox potentials tend to a significant oxidizing state. It is suggested that increased ROS level is associated with the development

ROS plays a controversial role in adipogenesis. On the one hand, ROS is a required signal molecule in the activation of key transcription factors responsible for adipogenesis. On the

It is originally identified that ROS is produced physiologically during adipogenesis. In the last decades, accumulating data prove that endogenously generated ROS acts as an essential mediator for adipogenic differentiation. Compared with that of preadipocytes, adipocytes have a relatively higher rate of spontaneous intra- and extracellular ROS production. Adipogenic hormonal cocktails could increase ROS production in preaipocytes and enhance the process of differentiation. C/EBPβ and PPARγ are the main factors that mediate the proadipogenic effect

It is shown that oxidative stress inhibits fat cell formation by reducing the C/EBP DNAbinding activity [5]. Mitochondrial ROS could inhibit preadipocyte proliferation, indicating that it can influence adipocyte differentiation through inhibiting MCE. In 3T3-F442A

other hand, ROS may also act as a negative regulator of the formation of adipocytes.

indicates white adipocyte differentiation here.

182 Redox - Principles and Advanced Applications

**adipogenesis**

**2.1. ROS and adipogenesis**

of ROS.

**2.2. ROS is a signal required for adipogenesis**

In a cell, ROS are mainly generated by mitochondrial respiration system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, endoplasmic reticulum (ER), and certain metabolic and detoxifying enzymes. Effect of ROS-producing systems on adipocyte differentiation is shown in **Figure 3**.
