A Creb3L Transcription Factor Coordinates ER Function Upon Food Intake to Regulate Lipid Metabolism

2021 ◽  
Author(s):  
Haris A. Khan ◽  
Ming Toh ◽  
Sonja Mühlberger ◽  
Tamas Schauer ◽  
Rory J. Beresford ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lipid Metabolism ◽  
Food Intake ◽  
Regulate Lipid Metabolism

scholarly journals A Creb3-Like Transcription Factor Coordinates ER Function upon Food Intake to Regulate Lipid Metabolism

2021 ◽  
Author(s):  
Haris A. Khan ◽  
Ming Toh ◽  
Tamás Schauer ◽  
Rory J. Beresford ◽  
Paula Ortega-Prieto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lipid Metabolism ◽  
Feeding Behavior ◽  
Transcriptional Activation ◽  
Feedback Loop ◽  
Protein Sorting ◽  
Nutrient Storage ◽  
Intracellular Organelle ◽  
Evolutionarily Conserved ◽  
Regulate Lipid Metabolism

SUMMARYIngestion of nutrients elicits essential physiological responses, including absorption, digestion, cessation of feeding and nutrient storage. The endoplasmic reticulum (ER) is central to this nutritional homeostasis, since it regulates intracellular organelle function, drives intercellular communication and promotes metabolite distribution. We identified theDrosophilaCreb3L-family transcription factor, CrebA, as the key metabolic regulator of ER function, thereby affecting lipid metabolism and feeding behavior. In response to feeding, CrebA activity is rapidly and transiently activated. CrebA directly drives the expression of the ER protein sorting machinery. We demonstrate that CrebA levels regulate lipid metabolism through lipoprotein secretion into the hemolymph and suppress feeding behavior. Further, CrebA mouse homologs are also upregulated in the liver following feeding and drive the transcriptional activation of ER protein sorting machinery genes in mammals. Our results reveal an evolutionarily conserved transcription switch which is turned on in response to food ingestion and orchestrates a negative feedback loop that promotes satiety by regulating ER function and protein secretion.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

scholarly journals Hepatocyte-specific Sirt6 deficiency impairs ketogenesis

2018 ◽  
Vol 294 (5) ◽  
pp. 1579-1589 ◽  
Author(s):  
Lei Chen ◽  
Qinhui Liu ◽  
Qin Tang ◽  
Jiangying Kuang ◽  
Hong Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Hepatic Lipid Metabolism ◽  
Camp Response Element ◽  
Hepatic Lipid ◽  
Element Binding Protein ◽  
Regulate Lipid Metabolism

Sirt6 is an NADH (NAD+)-dependent deacetylase with a critical role in hepatic lipid metabolism. Ketogenesis is controlled by a signaling network of hepatic lipid metabolism. However, how Sirt6 functions in ketogenesis remains unclear. Here, we demonstrated that Sirt6 functions as a mediator of ketogenesis in response to a fasting and ketogenic diet (KD). The KD-fed hepatocyte-specific Sirt6 deficiency (HKO) mice exhibited impaired ketogenesis, which was due to enhanced Fsp27 (fat-specific induction of protein 27), a protein known to regulate lipid metabolism. In contrast, overexpression of Sirt6 in mouse primary hepatocytes promoted ketogenesis. Mechanistically, Sirt6 repressed Fsp27β expression by interacting with Crebh (cAMP response element–binding protein H) and preventing its recruitment to the Fsp27β gene promoter. The KD-fed HKO mice also showed exacerbated hepatic steatosis and inflammation. Finally, Fsp27 silencing rescued hypoketonemia and other metabolic phenotypes in KD-fed HKO mice. Our data suggest that the Sirt6–Crebh–Fsp27 axis is pivotal for hepatic lipid metabolism and inflammation. Sirt6 may be a pharmacological target to remedy metabolic diseases.

scholarly journals The changes of chemerin and chemerin receptor to regulate lipid metabolism in liver and pituitary gland

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Sanggun Roh ◽  
Shun Kitayama ◽  
Astrid Ardiyanti ◽  
Yutaka Suzuki ◽  
Eri Yamauchi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Pituitary Gland ◽  
Regulate Lipid Metabolism

scholarly journals How cancer cells remodel lipid metabolism: strategies targeting transcription factors

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Do-Won Jeong ◽  
Seulbee Lee ◽  
Yang-Sook Chun
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Factors Associated ◽  
Modeling Techniques ◽  
Related Enzyme ◽  
Potential Strategy

AbstractReprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.

Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1

2020 ◽  
Vol 11 (3) ◽  
pp. 2418-2426 ◽  
Author(s):  
Mailin Gan ◽  
Linyuan Shen ◽  
Shujie Wang ◽  
Zhixian Guo ◽  
Ting Zheng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Target Genes ◽  
Obese Mice ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Regulate Lipid Metabolism

Genistein may regulate lipid metabolism in adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1.

Synthetic phosphoinositolglycans regulate lipid metabolism between rat adipocytesviarelease of GPI-protein-harbouring adiposomes

2010 ◽  
Vol 116 (3) ◽  
pp. 97-115 ◽  
Author(s):  
Günter Müller ◽  
Andrea Schulz ◽  
Elisabeth-Ann Dearey ◽  
Eva-Maria Wetekam ◽  
Susanne Wied ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Regulate Lipid Metabolism
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