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Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation
- Source :
- Biochemical Pharmacology. 122:42-61
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- SREBPs play important roles in the regulation of lipid metabolism, and are closely related to the occurrence and development of many metabolic diseases. Small molecular inhibitors of SERBPs are important tools in developing efficient treatment of metabolic diseases. However, there are no listing drug targeting SREBPs. Therefore, there is an urgent need to develop highly specific small molecules that inhibit SREBPs. In this study, using a hepatocyte-based high-throughput screening, we identified anhydroicaritin (AHI) as a novel inhibitor of SREBPs. HepG2, HL-7702, and human primary hepatocytes were used to verify the effects of AHI. We explored the mechanism by which AHI blocks the binding of SCAP/SREBPs complex with Sec23α/24D via regulating LKB1/AMPK/mTOR pathway. AHI reduced liver cell lipid level by preventing de novo lipogenesis. In diet induced obese mice, AHI ameliorated obesity, insulin resistance, fatty accumulation in liver and hyperlipemia. In conclusion, AHI improves diet-induced obesity and alleviates insulin resistance by suppressing SREBPs maturation which is dependent on LKB1/AMPK/mTOR pathway. Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cell Survival
Biology
Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Cell Line, Tumor
Internal medicine
medicine
Animals
Humans
Benzopyrans
Obesity
PI3K/AKT/mTOR pathway
Sterol Regulatory Element Binding Proteins
Pharmacology
Molecular Structure
TOR Serine-Threonine Kinases
Liver cell
Adenylate Kinase
Intracellular Signaling Peptides and Proteins
Membrane Proteins
AMPK
Lipid metabolism
medicine.disease
respiratory tract diseases
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
030220 oncology & carcinogenesis
Hepatocyte
Lipogenesis
lipids (amino acids, peptides, and proteins)
Insulin Resistance
Diet-induced obese
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....8edfd5604b126271474a10e871677714