Inflammation and Oxidative Stress in an Obese State and the Protective Effects of Gallic Acid

Phiwayinkosi V Dludla, Bongani B Nkambule, Babalwa Jack, Zibusiso Mkandla, Tinashe Mutize, Sonia Silvestri, Patrick Orlando, Luca Tiano, Johan Louw, Sithandiwe E Mazibuko-Mbeje, Phiwayinkosi V Dludla, Bongani B Nkambule, Babalwa Jack, Zibusiso Mkandla, Tinashe Mutize, Sonia Silvestri, Patrick Orlando, Luca Tiano, Johan Louw, Sithandiwe E Mazibuko-Mbeje

Abstract

Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, improve insulin signaling, and concomitantly combat raised pro-inflammatory response and oxidative stress. This review will revise mechanisms involved in the pathophysiological effects of inflammation and oxidative stress in an obese state. To better inform on its therapeutic potential and improvement of human health, available evidence reporting on the anti-obesity properties of gallic acid and its derivatives will be discussed, with emphases on its modulatory effect on molecular mechanisms involved in insulin signaling, inflammation and oxidative stress.

Keywords: gallic acid; inflammation; insulin resistance; obesity; oxidative stress; therapeutic target.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Overnutrition, sedentary lifestyle and genetic susceptibility are the leading factors associated with the development of obesity. In addition to dysfunctional angiogenesis, an obese state is characterized by an abnormal inflammatory response, low antioxidant capacity and reduced insulin sensitivity that may eventually lead to the generation of inflammation, oxidative stress and insulin resistance. The figure was modified from the following website, https://mexicobariatriccenter.com/improve-adipose-tissue-function/.
Figure 2
Figure 2
An obese state is associated with dysfunctional lipid metabolism including excessive lipolysis, which in turn leads to increased production and secretion of free fatty acids (FFAs). Elevated FFA levels can cause an abnormal pro-inflammatory response, and subsequent development of insulin resistance. Whereas, depleted intracellular antioxidant systems in the adipose tissue, mainly due to increased production of reactive oxygen species (ROS) can generate oxidative stress, and this can further lead to the development of insulin resistance. NADPH, nicotinamide adenine dinucleotide phosphate.
Figure 3
Figure 3
Chemical structures of gallic acid and its derivative compounds, including epigallocatechin gallate, ethyl gallate, gallocatechin gallate, methyl gallate, propyl gallate, theaflavin-3-gallate that are increasingly studied for their anti-obesity properties.
Figure 4
Figure 4
In addition to tea, avocado, blackcurrant, grapes, guava, mango, mulberry and pomegranate are some plants rich in gallic acid or its derivative compounds that are increasingly investigated for their anti-obesity properties. The following websites were used for the extraction of images: Tea, https://www.coffeebean.com/cafe-menu/tea; Avocado, https://draxe.com/avocado-benefits/; Grapes, https://www.indiamart.com/proddetail/purple-grapes-16445565830.html; Guava, https://exoticflora.in/products/guava-red-flesh-fruit-plants-tree; Mango, http://www.adagio.com/flavors/mango.html; Blackcurrant, https://tmbnotes.co/BlackcurrantMentholConcentrate; Mulberry, https://www.amazon.com/Dwarf-Everbearing-Mulberry-Plant-Morus/dp/B008BB8VOW; Pomegranate, https://www.organicfacts.net/health-benefits/fruit/health-benefits-of-pomegranate.html.

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