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Dietary Oxysterol, 7-Ketocholesterol Accelerates Hepatic Lipid Accumulation and Macrophage Infiltration in Obese Mice
- Source :
- Frontiers in Endocrinology, Frontiers in Endocrinology, Vol 11 (2021)
- Publication Year :
- 2020
-
Abstract
- Non-alcoholic fatty liver disease is strongly associated with obese and type 2 diabetes. It has been reported that an oxidized cholesterol, 7-ketocholesterol (7KC), might cause inflammatory response in macrophages and plasma 7KC concentration were higher in patients with cardiovascular diseases or diabetes. Therefore, we have decided to test whether small amount of 7KC in diet might induce hepatic steatosis and inflammation in two types of obese models. We found that addition of 0.01% 7KC either in chow diet (CD, regular chow diet with 1% cholesterol) or western type diet (WD, high fat diet with 1% cholesterol) accelerated hepatic neutral lipid accumulation by Oil Red O staining. Importantly, by lipid extraction analysis, it has been recognized that triglyceride rather than cholesterol species was significantly accumulated in CD+7KC compared to CD as well as in WD+7KC compared to WD. Immunostaining revealed that macrophages infiltration was increased in CD+7KC compared to CD, and also in WD+7KC compared to WD. These phenotypes were accompanied by inducing inflammatory response and downregulating fatty acid oxidation. Furthermore, RNA sequence analysis demonstrated that 7KC reduced expression of genes which related to autophagy process. Levels of LC3-II protein were decreased in WD+7KC compared to WD. Similarly, we have confirmed the effect of 7KC on acceleration of steatohepatitis in db/db mice model. Collectively, our study has demonstrated that small amount of dietary 7KC contributed to accelerate hepatic steatosis and inflammation in obese mice models.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
obesity
autophagy
Oxysterol
Endocrinology, Diabetes and Metabolism
Mice, Obese
steatohepatitis
Inflammation
macrophage
lcsh:Diseases of the endocrine glands. Clinical endocrinology
Cholesterol, Dietary
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Oil Red O
Animals
Ketocholesterols
7-ketocholesterol
Original Research
lcsh:RC648-665
Triglyceride
Cholesterol
Macrophages
Fatty liver
Body Weight
Oxysterols
medicine.disease
030104 developmental biology
chemistry
Liver
030211 gastroenterology & hepatology
Steatosis
medicine.symptom
Steatohepatitis
Inflammation Mediators
Subjects
Details
- ISSN :
- 16642392
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in endocrinology
- Accession number :
- edsair.doi.dedup.....2bf2397c81411249cb46e60e88165de3