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Review
. 2024 Sep 4;19(1):120.
doi: 10.1186/s13020-024-00988-w.

Targeting lipid droplets and lipid droplet-associated proteins: a new perspective on natural compounds against metabolic diseases

Xinyue Jiang #  1 , Hongzhan Wang #  1 , Kexin Nie  1 , Yang Gao  1 , Shen Chen  1 , Yueheng Tang  2 , Zhi Wang  3 , Hao Su  3 , Hui Dong  4
Affiliations
Review

Targeting lipid droplets and lipid droplet-associated proteins: a new perspective on natural compounds against metabolic diseases

Xinyue Jiang et al. Chin Med. .

Abstract

Background: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins.

Methods: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized.

Results: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases.

Conclusion: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.

Keywords: Lipid droplet; Lipid droplet-associated proteins; Metabolic diseases; Natural compounds.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
LD biogenesis. Activated fatty acids produce neutral lipids in TAG synthesis. Wrapped by the phospholipid molecule shell deriving from the ER leaflets, the neutral lipids sprout into oil lenses and grow larger. When the superficial tension attains a certain level, the budding LD flips form a mature LD
Fig. 2
Fig. 2
LD growth and LD degradation. A 1. When LDs contact with ER, adipogenic enzymes catalyze the TAG synthesis. 2&3. Both LD fusion and lipid transfer between LDs render the growth. B 1. Macroautophage is the process of formation of autophagosome by double-membrane vacuoles before fusion with lysosomes. 2. Chaperon-mediated autophagy (CMA) refers to lysosomal selective capture of LDs containing the KFERQ motif. 3. Direct lysosomal degradation of LDs is microautophagy
Fig. 3
Fig. 3
Abnormal LD formation in metabolism-related diseases. The FASN-mediated lipid synthesis system and CIDE-mediated LD fusion promote the generation of giant LDs. Moreover, the expression of ATGL, CGI8, Rab7/18, ACOX, CPT1, ABCA1, and ABCG1 is downregulated, inhibiting lipolysis and β-oxidation, resulting in LD deposition
Fig. 4
Fig. 4
Chemical structures and mechanism of natural compounds. (A) BBR; (B) MGF; (C) CAP; (D) CAF; (E) GEN; (F) EGCG; (G) CGA; (H) BET; (I) GIN; (J) RES. All the chemical structures were obtained from pubchem: https://pubchem.ncbi.nlm.nih.gov/
Fig. 5
Fig. 5
The effects of natural compounds on lipotoxicity-related metabolic diseases from the perspective of LD-associated proteins
See this image and copyright information in PMC

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