scholarly journals Crtc1 Deficiency Causes Obesity Potentially via Regulating PPARγ Pathway in White Adipose

2021 ◽  
Vol 9 ◽  
Author(s):  
Yimeng Hu ◽  
Jian Lv ◽  
Yu Fang ◽  
Qiang Luo ◽  
Yuan He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Direct Interaction ◽  
Underlying Mechanism ◽  
Fat Accumulation ◽  
Glucose And Lipid Metabolism ◽  
White Adipocytes ◽  
Transcription Cofactor ◽  
Lipid Metabolism Disorders ◽  
Normal Feeding

Obesity is characterized by excessive fat accumulation and associated with glucose and lipid metabolism disorders. Crtc1, a transcription cofactor regulating CREB activity, has been involved in the pathogenesis of metabolic syndrome; however, the underlying mechanism remains under debate. Here we generated a Crtc1–/– mouse line using the CRISPR/Cas9 system. Under normal feeding conditions, Crtc1–/– mice exhibited an obese phenotype resultant from the abnormal expansion of the white adipocytes. The development of obesity in Crtc1–/– mice is independent of alterations in food intake or energy expenditure. Moreover, Crtc1–/– mice were more prone to insulin resistance and dyslipidemia, as evidenced by higher levels of plasma glucose, insulin and FABP4 than wildtype mice. Transcriptome analysis in liver and epididymal white adipose tissue (eWAT) showed that the fat accumulation caused by Crtc1 deletion was mainly related to lipid metabolism in adipose tissue, but not in liver. GSEA and KEGG analysis identified PPAR pathway to be of the highest impact on lipid metabolism in eWAT. This regulation was independent of a direct interaction between CRTC1 and PPARγ. Our findings demonstrate a crucial role of Crtc1 in regulating lipid metabolism in adipose during development, and provide novel insights into obesity prevention and therapeutics.

scholarly journals Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat

2006 ◽  
Vol 91 (11) ◽  
pp. 4287-4294 ◽  
Author(s):  
Tania S. Burgert ◽  
Sara E. Taksali ◽  
James Dziura ◽  
T. Robin Goodman ◽  
Catherine W. Yeckel ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Visceral Fat ◽  
Resonance Imaging ◽  
Fat Accumulation ◽  
Glucose And Lipid Metabolism ◽  
The Metabolic Syndrome ◽  
Hepatic Fat ◽  
Fat Fraction

Abstract Background: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established. Methods: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging. Findings: Elevated ALT (>35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18–35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver. Interpretation: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.

Effects of VO2 nanoparticles on human liver HepG2 cells: Cytotoxicity, genotoxicity, and glucose and lipid metabolism disorders

NanoImpact ◽  
2021 ◽  
Vol 24 ◽  
pp. 100351
Author(s):  
Jia-Bei Li ◽  
Wen-Song Xi ◽  
Shi-Ying Tan ◽  
Yuan-Yuan Liu ◽  
Hao Wu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders

SEX DIFFERENCES OF CARBOHYDRATE AND LIPID METABOLISM IMPAIRMENT IN RATS WITH TYPE 2 DIABETES MELLITUS

2018 ◽  
Vol 64 (2) ◽  
pp. 39-45 ◽  
Author(s):  
Nataliia Gorbenko ◽  
Oleksii Borikov ◽  
Olha Ivanova ◽  
K. V. Taran ◽  
T. S. Litvinova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Lipid Metabolism ◽  
Female Rats ◽  
Glucose And Lipid Metabolism ◽  
Carbohydrate And Lipid Metabolism ◽  
Lipid Metabolism Disorders

A sex difference of carbohydrate and lipid metabolism disorders in rats with type 2 diabetes has been studied. It was established that type 2 diabetes leads to a more pronounced deterioration in carbohydrate toleranceand insulin sensitivity in males compared to female rats, but the sex doesn’t affect basal glycemia and fructosamine levels. It was found that the increase of body weight and visceral fat in rats with type 2 diabetes is moremanifested in females than in males. It has been determined that hypertriglyceridemia is higher in diabeticmales compared to diabetic females, and the level of common lipids in the liver, both intact females and femaleswith type 2 diabetes, is lower than that of the males. The obtained results indicate a more expressive impairment of glucose and lipid metabolism in males compared to females with type 2 diabetes

Chlorpyrifos exposure induces lipid metabolism disorder at the physiological and transcriptomic levels in larval zebrafish

2019 ◽  
Vol 51 (9) ◽  
pp. 890-899
Author(s):  
Xiaoyu Wang ◽  
Jiajie Zhou ◽  
Manlu Shen ◽  
Jiayan Shen ◽  
Xinyue Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Acid Synthesis ◽  
Treated Group ◽  
Heart Tissue ◽  
Lipid Metabolism Disorder ◽  
Larval Zebrafish ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Cellular Apoptosis

Abstract Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 μg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.

scholarly journals Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes

2016 ◽  
Vol 310 (7) ◽  
pp. E550-E564 ◽  
Author(s):  
Ana Burgeiro ◽  
Amelia Fuhrmann ◽  
Sam Cherian ◽  
Daniel Espinoza ◽  
Ivana Jarak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Glucose Uptake ◽  
Epicardial Adipose Tissue ◽  
Heart Failure Patients ◽  
Fat Depots ◽  
Glucose And Lipid Metabolism

Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [14C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased ( P = 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant ( P < 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.

scholarly journals Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yue Li ◽  
Xin Yang ◽  
Jing Zhang ◽  
Tianyi Jiang ◽  
Ziyi Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Ketogenic Diet ◽  
Glucose Intolerance ◽  
Lipid Accumulation ◽  
Fat Accumulation ◽  
Glucose And Lipid Metabolism ◽  
Ketogenic Diets

ABSTRACT The ketogenic diet (KD), which can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive. Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. And the KD widely used in human studies still induced insulin resistance and fat accumulation in mice. Moreover, KDs changed the gut microbiota and metabolites in mice, and the sources and proportions of fat in the diets respectively changed the abundance of specific bacteria and metabolites which were correlated with parameters related to glucose intolerance and lipid accumulation. Overall, our study demonstrated that the metabolic disorders induced by KDs are closely related to the source and proportion of fat in the diet, which may be associated with the changes of the gut microbiota and metabolites. IMPORTANCE The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. Here, we surveyed the effects of two ketogenic diets which are commonly used in mouse trials on metabolic phenotypes, gut microbiota, and metabolites in mice. We found that both ketogenic diets impaired glucose and lipid metabolism in mice, and this may be due to the sources and proportions of fat in the diets. This work highlights the potential risk of glucose and lipid metabolism disorders and the importance of evaluating the sources and proportions of fat in the diets, when using ketogenic diets for weight loss and the treatment of diseases.

scholarly journals Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice

2021 ◽  
Vol 12 (8) ◽  
pp. 1267-1281
Author(s):  
Ayiguli Alimu ◽  
Haiqiemuhan Abudureman ◽  
Yong-Zhi Wang ◽  
Mei-Yan Li ◽  
Jia-Sui Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Decabromodiphenyl Ether ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders
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