Abstract
Epidemiological and preclinical studies have demonstrated that bioactive foods like flavonoids, polyphenolic compounds derived from fruits and vegetables, exert a protective action against obesity, cardiovascular disorders, and Adipocyte Tissue Macrophage infiltration (ATM). All these pathologies are characterized by increase in reactive oxygen species (ROS) and in proinflammatory cytokines that have been shown to favor the migration of immune cells, particularly of macrophages, in metabolically active organs like the liver and adipose tissue, that in Drosophila are constituted by a unique organ: the fat body. This study, using a unique Drosophila model that mimics human ATM, reveals the beneficial effects of flavonoids to reduce tissue inflammation. Our data show that anthocyanin-rich food reduces the number of hemocytes, Drosophila macrophages, infiltrating the fat cells, a process that is associated with reduced production of ROS and reduced activation of the JNK/SAPK p46 stress kinase, suggesting a fundamental function for anthocyanins as antioxidants in chronic inflammation and in metabolic diseases.
Highlights
Obesity is a metabolic syndrome occurring worldwide and often associated with other chronic diseases such as cardiovascular disorders, type II diabetes, and cancer [1].The onset of obesity is the result of multifactorial elements, including a sedentary lifestyle, genetic predisposition, ethnicity, and environmental factors [2]; these factors with a diet rich in fats and sugars and poor in phytonutrients may result in weight gain and subsequently lead to metabolic disorders [3, 4]
Chronic inflammation in the adipose tissue is characterized by the infiltration of macrophages in the fat cells; we analyzed if a similar event was present in the FB of our obese animals
These results showed that FBs from P Gal /Hml-Red Fluorescence Protein (RFP); UAS-Ni animals contain at 5 days AEL a small but significantly higher number of hemocytes in their FBs (5.2%, P < 0.05) as compared to control P Gal /Hml-RFP (Figure 1(e)); at 12 days the percentage of hemocytes in P -Gal /Hml-RFP; UAS-Ni animals was drastically increased to 17% (P < 0.00001)
Summary
Obesity is a metabolic syndrome occurring worldwide and often associated with other chronic diseases such as cardiovascular disorders, type II diabetes, and cancer [1].The onset of obesity is the result of multifactorial elements, including a sedentary lifestyle, genetic predisposition, ethnicity, and environmental factors (such as organic pollutants) [2]; these factors with a diet rich in fats and sugars and poor in phytonutrients may result in weight gain and subsequently lead to metabolic disorders [3, 4]. The adipose tissue regulates lipid homeostasis and in normal conditions controls the storage of energy reserves in the form of triglycerides as well as functioning as an endocrine organ, producing a variety of proinflammatory cytokines such as IL-1, IL-6, and IL-8, IFNγ, and TNFα [11, 12] In pathological conditions, such as obesity or metabolic syndrome, the adipocytes start to alter the production of these proinflammatory cytokines, which results in the activation of the innate immune system with recruitment of immune cells including macrophages leading to a state of chronic inflammation or ATM [7]. This pathway is highly conserved in Drosophila and consists of a cascade of phosphorylation events starting with the activation of the JNKKK kinases, consisting of the Ask and Tak, that activate MKK7, the orthologue of Hemipterous (Hep), and terminates with the activation of JNK/SAPK p46 kinase, called basket (bsk) in Drosophila, that is negatively regulated by Puckered (puc), a BioMed Research International phosphatase, which itself is a target of JNK/SAPK p46 kinase (see Figure 3(e)) [16]
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