Natural alkaloid and polyphenol compounds targeting lipid metabolism: Treatment implications in metabolic diseases

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Abstract

Once the balance between lipid anabolism and catabolism is broken, metabolic disorder will occur in the organism and finally lead to metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD), obesity and cancer. No established therapeutic regimens for treating NAFLD and obesity exist yet. Many natural compounds are extracted from botany, fungi and marine organisms. Importantly, natural compounds are major sources of innovative medicine. In this review, we first elucidate the important roles of lipid metabolism in NAFLD, obesity and cancer. Next, we summarize the action mechanisms of natural compounds including alkaloid, polyphenol targeting lipid metabolism. Therefore, manipulating lipid metabolism to reduce fatty acid availability may be the starting point for improving or even curing lipid metabolism-related diseases. Alkaloid and polyphenol are promising candidates for metabolic diseases to ameliorate lipid metabolism abnormalities.

Introduction

Metabolism is the process by which organism continuously exchanges substance and energy with environment, finally realizes self-renewal. Metabolism is usually divided into two categories: anabolism (assimilation) and catabolism. Lipids provide the energy and essential fatty acids for our body. Lipids are also indispensable components of cells and tissues, such as cell membranes and myelin. Therefore, abnormalities in lipid anabolism or catabolism can lead to pathological changes in the body, such as obesity, nonalcoholic fatty liver disease (NAFLD) and even tumor (Ferrara et al., 2019; Ojulari et al., 2019).

Obesity is always defined as excess of fat mass, which increases risks for multiple chronic diseases, including cardiovascular disease, type 2 diabetes, and several types of cancer (Guglielmi and Sbraccia, 2018). There is a close relationship between lipid metabolism and obesity. The main repository for energy in humans is white adipose tissue (WAT)(Frayn et al., 2003). WAT has a high degree of heterogeneity (Schoettl et al., 2018; Wronska and Kmiec, 2012), which mainly stores in subcutaneous (SC) abdominal and glutealā€“femoral region. Under the obese condition, these depot-specific differences translate into specific adipose distribution patterns. Many studies have shown that WAT metabolic disorders in SC may cause decreased self-renewal and division, eventually leading to cell hypertrophy (Kim et al., 2014; Guglielmi and Sbraccia, 2018). In addition, during the development of obesity, fibrosis of WAT may limit the expansion of WAT and the flexibility of lipid storage, which leads to ectopic storage of lipids (Khan et al., 2009). Thereby, lipid metabolism plays an important role in the development of obesity.

NAFLD represents a series of diseases caused by excessive accumulation of fat in the liver (Esler and Bence, 2019), and its prevalence and diagnosis are on the rise worldwide. Liver steatosis is the first step in NAFLD and is characterized by the influx of large amounts of fat from inflamed adipose tissue (AT), which increases liver fat production and reduces fat catabolism. Lipid accumulation of hepatocytes leads to fatty toxicity, persistent oxidation and endoplasmic reticulum stress, making them more susceptible to cell death. Due to liver injury and inflammatory immune cell activation/recruitment, further deterioration of NAFLD will develop into more severe nonalcoholic steatohepatitis (NASH) and even hepatic carcinoma (Luci et al., 2019; Esler and Bence, 2019).

Cancer cells often exhibit fundamentally altered cellular metabolism, which provides a biochemical basis and directly leads to tumorigenesis and malignancy (Benjamin et al., 2012; Kaelin and Thompson, 2010; Luo et al., 2018a, 2019b). Recently, more and more researches have shown that lipid metabolism is significantly activated during carcinogenesis and malignant progression of tumors (Tan et al., 2018; Luo et al., 2017, 2018b). Changes in lipid metabolism can affect the progression of many tumor cells, including cell growth, proliferation, differentiation, and migration (Santos and Schulze, 2012; Luo et al., 2019a). In cancer cells, enhanced de novo fatty acid synthesis is principally used for membrane formation, energy storage, and signal molecule production.

In summary, the disorder of lipid metabolism can cause serious diseases and some complications. Therefore, regulating lipid metabolism may be the starting point for improving or even curing lipid metabolism-related diseases. Many natural compounds are extracted from botany, fungi and marine organisms. Importantly, natural compounds are major source of innovative medicine (Liao et al., 2019; Cheng et al., 2019; Luo et al., 2016). Here, we summarize the reported alkaloid and polyphenols natural compounds involved in the regulation of lipid metabolism, and clarify the mechanism by which each species of natural compound ameliorates metabolic disease through targeting lipid metabolism (Fig. 1).

Section snippets

Alkaloids and lipid metabolism

Alkaloids are alkaline nitrogenous organic compounds, which widely exist in natural plants. Most alkaloids have complex cyclic structures and exhibit significant activities in lipid metabolism (Table 1).

Polyphenols and lipid metabolism

Polyphenolic compounds refer to a group of chemical substances found in plants that collectively contain multiple phenolic groups. Polyphenols possess beneficial anti-oxidation function, promote digestion of the stomach, lower blood fat and blood pressure, enhance human immunity, prevent arteriosclerosis and thrombosis, and inhibit the growth of bacteria and cancer (Cai et al., 2015). Here, we describe several polyphenols, including mangiferin, resveratrol, curcumin and

Conclusion

Lipid anabolism and catabolism are in dynamic equilibrium in healthy organism. Once this balance is broken, diseases associated with abnormal lipid metabolism will occur (Han and Wang, 2018). In NAFLD, obesity and cancer, de novo lipogenesis are increased, while compensatory enhancement of FAO is insufficient in normalizing lipid levels, eventually leading to excessive lipid accumulation (Softic et al., 2016).

Alkaloids and polyphenols mentioned in this review have been demonstrated to

Grant support

This work was supported by grants from the National Natural Science Foundation of China (81874195, 81573014).

Author agreement

All the authors are aware of and agree to the contents of the paper and their being listed as an author on the manuscript.

Declaration of competing interest

The authors declare that they have no potential conflicts of interest related to the contents of this article.

Acknowledgements

None.

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