Knockdown of long non‐coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non‐alcoholic fatty liver disease

Autor: Zhi Yue, Lei Meng, Yueshuang Hu, Tonghuan Li, Xia Huang
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Clinical Biochemistry
Down-Regulation
digestive system
Biochemistry
Diabetes Mellitus
Experimental
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Non-alcoholic Fatty Liver Disease
Internal medicine
medicine
Animals
RNA
Small Interfering
Triglycerides
Gene knockdown
biology
Triglyceride
Chemistry
Fatty liver
nutritional and metabolic diseases
Lipid metabolism
Cell Biology
General Medicine
Lipid Metabolism
medicine.disease
Up-Regulation
Disease Models
Animal
Fatty acid synthase
Glucose
030104 developmental biology
Endocrinology
Liver
Gluconeogenesis
030220 oncology & carcinogenesis
Hepatocytes
biology.protein
RNA Interference
RNA
Long Noncoding
Steatosis
Sterol Regulatory Element Binding Protein 1
Phosphoenolpyruvate Carboxykinase (ATP)
Zdroj: Cell Biochemistry and Function. 38:839-846
ISSN: 1099-0844
0263-6484
DOI: 10.1002/cbf.3495
Popis: Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long non-coding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. SIGNIFICANCE OF THE STUDY: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.
Databáze: OpenAIRE
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