Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the
impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis
and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to Healthy diets is highly encouraged because of which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties.
Oxidative Stress and Inflammation Interplay in Obesity
The etiology of obesity is multifactorial. Nevertheless, systemic oxidative stress, resulting from the impaired antioxidant defense system counteracting reactive oxygen species (ROS), is a major hallmark of obesity. Indeed, superoxide anion (O2•-) overproduction during obesity can result from protein kinase C (PKC) activation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), glyceraldehyde auto-oxidation and
oxidative phosphorylation. Moreover, chronic inflammation has been demonstrated to be associated with oxidative stress in obesity. Protein oxidation and protein misfolding result in adipocyte proteasomal dysfunction. This latter leads to insulin resistance, mediated by obesity-induced endoplasmic reticulum (ER) stress in the liver. Thus, reactive oxygen species (ROS) overproduction during mitochondrial stress is associated with exacerbated inflammation and insulin resistance in adipocytes through the activation of NF- κB. NF-κB is a transcriptional factor that regulates cytokine gene expression and the inflammatory response, and it can be activated by a variety of stimuli, including dietary or endogenous lipids, hypoxia and gut-derived antigens. Hence, NF-κB seems to serve as a bridge between inflammation and obesity.
Oxidative stress occurs as a result of an imbalance between endogenous reactive oxygen species (ROS) production and the natural antioxidant system. Indeed, it has been reported that obesogenic high-fat Western diets induce a drastic increase in oxidative stress and inflammation associated with insulin resistance and hyperglycemia. In fact, high glucose intake increases reactive oxygen species (ROS) generation by mononuclear cells and inflammation, revealed by an increase in NF-κB and activator protein-1 (AP-1) activities in healthy human subjects. Hyperglycemia constitutes the onset of advanced glycation end products (AGEs)-mediated oxidative stress. Furthermore, the excess of nutrients such as glucose and free fatty acids (FFAs) leads to the activation of NADPH oxidase (NOX) in adipocytes. NADPH oxidase (NOX), which can also be activated by PKC, triggers adipogenesis in preadipocytes and mediates intracellular reactive oxygen species reactive oxygen species (ROS) generation, particularly of O2•-, in non-phagocytic cells. PKC and NOX can, in turn, be activated by H2O2 in adipocytes. In addition to NOX-mediated intracellular reactive oxygen species (ROS) production, there is evidence that the mitochondrial respiratory chain is the principal source of cellular reactive oxygen species (ROS), resulting in exacerbated oxidative stress and inflammatory processes in obesity. Reactive oxygen species (ROS) and oxidative stress are known for the activation of stress-activated protein kinases (SAPKs, also referred to as the c-Jun N-terminal kinases, JNKs). IκB kinase β (IKKβ) has also been shown to be regulated by oxidative stress and pro-oxidants. After being activated, all of these kinases trigger pro-inflammatory cytokines, chiefly through the nuclear translocation of NF-κB and AP-1 transcription factors in adipose tissue cells. It is well known that these proteins regulate gene expression of several oxidant-responsive adipokines such as TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI- 1). It has been demonstrated that IKK-dependent TNF-α activation downregulates AMPK, which plays a pivotal role in energy homeostasis and modulation of metabolic inflammation. Increased AMPK phosphorylation has been correlated with enhanced anti-inflammatory, adiponectin-dependent PPARγ expression and decreased expression of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2). Therefore, it has been suggested that NF-κB-mediated inflammatory pathways in adipocytes involve the activation of COX-2 and PGE2 signaling and hypoxia associated with the decrease in anti-inflammatory, adiponectin and PPARγ expression. TNF-α and IL-6 secreted from white adipose tissue (WAT)are responsible for the onset of inflammation in other tissues and organs, such as the liver where they enhance hepatic C-reactive protein (CRP) expression. Furthermore, circulating MCP-1 (also called CCL2 for chemokine C-C motif ligand 2), which is expressed and secreted from both adipocytes and activated macrophages, promotes monocyte migration and infiltration into WAT across the endothelium. A crosstalk between adipocytes and resident macrophages reinforces oxidative stress through TNF-α–mediated ROS generation within WAT cells in an autocrine and paracrine manner. Taken together, all of these events result in local and systemic low-grade inflammation, which can lead to multiple pathogenic outcomes ranging from type 2 diabetes to pro-oncogenic events associated with obesity.
Antioxidant nutraceuticals in Healthy diets
Healthy diets are characterized by greater intake of whole cereal grains, fruits, vegetables, legumes and nuts; low intake of red meat; and sweets and salty food. Various studies have demonstrated that Healthy diets provide high levels of phytochemicals, including dietary polyphenols, which have been reported to exert beneficial biological effects, including antioxidant, anti-inflammatory, immunomodulatory, antitumoral, antidiabetic and anti-obesity activities.
On the basis of a randomized intervention trial, it has been suggested that bioactive polyphenols in Healthy diets may improve low-grade chronic inflammatory states. Numerous studies have reported that polyphenols are the most abundant antioxidants in Healthy diets. Phenolic acids, such as gallic, ferulic and other hydroxycinnamic acid derivatives, are found in a variety of foods, including whole grains, fruits, vegetables, nuts. Flavonoids, with about 6000 molecules, are the largest group of polyphenols. Flavonoids exert prominent antioxidant and anti-inflammatory activities through various mechanisms. In addition to their role in food intake regulation and nutrition absorption, a growing body of evidence supports that flavonoids increase adiponectin and AMPK activation and counteract NF- κB and inducible nitric oxide synthase (iNOS) signaling pathways, resulting in reduced oxidative damage and inflammation associated with obesity.
Karimi, H.
Master of clinical Nutrition & Dietetics
Reference
-Nani A, et al. Antioxidant and Anti-Inflammatory Potential of Polyphenols
Contained in Mediterranean Diet in Obesity:
Molecular Mechanisms.Molecules.2021.
