Abstract

Oxidative stress and inflammation in hypertrophied adipose tissue with excessive fat accumulation play a crucial role in the development of obesity and accompanying metabolic dysfunctions. This study demonstrated the capacity of elderberry fruit (EDB) extract to decrease the elevated production of reactive oxygen species in hypertrophied 3T3-L1 adipocytes. Treatment with the EDB extract resulted in modulation of mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression of leptin and adiponectin was, respectively, down- and up-regulated. Moreover, glucose uptake stimulation was noticed in mature adipocytes, both sensitive to insulin and insulin resistant. This may suggest a positive effect of EDB extract on insulin resistance status. The extract was also found to alleviate the inflammatory response in activated RAW 264.7 macrophages by down-regulating the expression of proinflammatory genes (TNF-α, IL-6, COX-2, iNOS) and suppressing the enhanced production of inflammatory mediators (TNF-α, IL-6, PGE2, NO). In vitro experiments showed that the EDB extract could inhibit digestive enzymes, including α-amylase, α-glucosidase, and pancreatic lipase, leading to reduced intestinal absorption of dietary lipids and carbohydrates. Further in vivo studies could be postulated to support EDB as a functional food component for the prevention and treatment of obesity and metabolic-immune comorbidities.

Highlights

  • Obesity is associated with excessive adipose tissue growth, which occurs through two possible mechanisms: hypertrophy and hyperplasia

  • The decrease in PGE2 production was detected after cell exposure to the extract

  • Excessive fat accumulation in hypertrophic adipose tissue associated with obesity is responsible for oxidative stress, chronic inflammation, and dysregulated adipokine secretion [25]

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Summary

Introduction

Obesity is associated with excessive adipose tissue growth, which occurs through two possible mechanisms: hypertrophy (expansion of existing adipocytes) and hyperplasia (recruitment of new adipocytes). Hypertrophic adipose tissue growth is mainly considered to be related to insulin resistance and other obesity metabolic comorbidities [1]. Abnormal expansion of adipose tissue is accompanied by local hypoxia, adipocyte death, enhanced cytokine and chemokine secretion, dysfunctional fatty acid metabolism and accumulation, and immune cell infiltration. Dysregulation of lipid metabolism in adipose tissue leads to enhanced release of free fatty acids, which initiates inflammatory signaling cascades in the infiltrating cell population. Chronic low-grade inflammation, found in abnormal fat tissue, negatively affects the insulin signal transduction pathway, and promotes insulin resistance [2,3].

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