Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N⁶-adenylate methylation (m⁶A) on RNA represents a new "post-transcriptional" regulation mode. m⁶A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m⁶A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m⁶A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.
Humans ; Methylation ; Epigenesis, Genetic ; Lipid Metabolism/genetics* ; Lipid Metabolism Disorders/genetics* ; Liver Neoplasms ; RNA

OBJECTIVE: To investigate the changes of lipid metabolism and stress response of adult C.elegans exposed to non-freezing low temperature and explore the possible mechanism. METHODS: The survival rate and activity of adult C.elegans cultured at 20℃ or 4℃ were observed.Lipid metabolism of the cultured adult C.elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism.The effects of low temperature exposure on stress level of adult C.elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels. RESULTS: The lifespan and activity of adult C.elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P < 0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1;P < 0.01).Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2(P < 0.05) but lowered the number of mitochondria (P < 0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1(P < 0.05).Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C.elegans to cold stress as shown by further reduced activity (P < 0.05) and reduced survival rate at 24 h (P < 0.0001) under cold stress. CONCLUSION Exposure to a low temperature at 4℃ results in lowered lipid metabolism of adult C.elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C.elegans.
Animals ; Antioxidants/metabolism* ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics* ; Cold-Shock Response ; Lipid Metabolism ; Lipid Metabolism Disorders ; Longevity/genetics*

In recent years, long non-coding RNA (lncRNA) has been proved to be involved in the regulation of biological processes at various levels, attracting research interests in life science. LncRNA possesses the unique capability and exert discrete effects on transcription, translation and post-translational modification of the target genes through interacting with DNA, RNA and protein. Current studies have revealed that lncRNA plays an important role in hepatic metabolism via diverse pathways. This review focuses on the function of lncRNA and its relationship with hepatic energy metabolism and the correlated diseases, to elucidate the underlying mechanisms and prospects of lncRNA researches.
Glucose/metabolism* ; Lipid Metabolism/genetics* ; Liver/metabolism* ; RNA, Long Noncoding/genetics*

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.
17-Hydroxysteroid Dehydrogenases ; genetics ; metabolism ; Animals ; Genome-Wide Association Study ; Genomics ; Humans ; Lipid Droplets ; metabolism ; Lipid Metabolism ; genetics ; Non-alcoholic Fatty Liver Disease ; genetics ; metabolism ; Proteomics

This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.
Adipose Tissue, Brown ; Animals ; Diabetes Mellitus, Experimental/genetics* ; Drugs, Chinese Herbal ; Fibronectins ; Glucose ; Lipid Metabolism ; Lipid Metabolism Disorders ; Rats

The gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ，to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.
Genes, ras ; Humans ; Lipid Metabolism/genetics* ; Neoplasms/genetics* ; Signal Transduction ; ras Proteins/metabolism*

Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
Animals ; Caenorhabditis elegans ; genetics ; metabolism ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Female ; Lipid Droplets ; metabolism ; Lipid Metabolism ; physiology ; Longevity ; physiology ; Mutation ; Oogenesis ; physiology

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.
Animals ; Energy Metabolism/genetics* ; Homeostasis ; Lipid Metabolism ; Signal Transduction ; Transcription Factors/metabolism*

As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved in various physiological processes in hepatic function as well as in liver pathology. There is now compelling evidence that miR-122, as a regulator of gene networks and pathways in hepatocytes, plays a central role in diverse aspects of hepatic function and in the progress of liver diseases. This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism. With regard to liver diseases, miR-122 was shown to stimulate hepatitis C virus (HCV) replication through a unique and unusual interaction with two binding sites in the 5'-UTR of HCV genome to mediate the stability of the viral RNA, whereas inhibit the expression and replication of hepatitis B virus (HBV) by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway. In addition, miR-122 acts as a suppressor of cell proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity. Notably, a clinical trial targeting miR-122 with the anti-miR-122 oligonucleotides miravirsen, the first miRNA targeted drug, has been initiated for treatment of HCV infection. With further understanding of the comprehensive roles of miR-122 in hepatic functions and the mechanisms involved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma, miR-122 appears to be a promising candidate for effective therapeutic approaches against tumor and infectious diseases.
Humans ; Lipid Metabolism ; genetics ; Liver ; growth & development ; metabolism ; physiopathology ; Liver Diseases ; genetics ; physiopathology ; MicroRNAs ; genetics ; metabolism ; Models, Biological

Humans ; Muscular Diseases/genetics* ; Cardiomyopathies/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Mutation ; Lipids ; Muscle, Skeletal ; Acyltransferases/genetics* ; Lipase/genetics*