Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance

2018 ◽  
Vol 120 ◽  
pp. 330-341 ◽  
Author(s):  
Shaohua Fan ◽  
Yanyan Wang ◽  
Cun Wang ◽  
Haojie Jin ◽  
Zheng Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Specific Deletion

scholarly journals Effect of the Hepatocyte-Specific Deletion of SND1 in Mice on the Liver Insulin Resistance and Acute Liver Failure

2020 ◽  
Author(s):  
Chunyan Zhao ◽  
Xiaoteng Cui ◽  
Baoxin Qian ◽  
Nan Zhang ◽  
Lingbiao Xin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cholesterol Level ◽  
Hepatic Steatosis ◽  
Glucose Homeostasis ◽  
Hepatic Failure ◽  
High Fat Diet ◽  
High Fat ◽  
Specific Deletion

Abstract Background: The multifunctional protein SND1 was reported to be involved in a variety of biological processes, such as cell cycle, proliferation or lipogenesis. We previously proposed that global-expressed SND1 in vivo is likely to be a key regulator for ameliorating HFD-induced hepatic steatosis and systemic insulin resistance. Herein, we are very interested in investigating further whether the hepatocyte-specific deletion of SND1 affects the insulin resistance or acute liver failure (ALF) of mice.Methods: By using Cre-loxP technique, we constructed conditional knockout (LKO) mice of SND1 driven by albumin in hepatocytes and analyze the changes of glucose homeostasis, cholesterol level, hepatic steatosis and hepatic failure under the treatment of high-fat diet (HFD) or upon the simulation of Lipopolysaccharide/galactosamine (LPS/GalN).Results: No difference for the body weight, liver weight, and cholesterol level was detected. Furthermore, we did not observe the alteration of glucose homeostasis in SND1 hepatic knockout mice on either chow diet or high-fat diet. Besides, hepatocyte-specific deletion of SND1 failed to influence the hepatic failure of mice induced by LPS/GalN.Conclusions: These findings suggest that hepatic SND1, independently, is insufficient for changing glucose homeostasis, hepatic lipid accumulation and inflammation. The synergistic action of multiple organs may contribute to the role of SND1 in insulin sensitivity or inflammatory response.

scholarly journals Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity

2015 ◽  
Vol 308 (6) ◽  
pp. E460-E469 ◽  
Author(s):  
Zheng Chen ◽  
Hong Shen ◽  
Chengxin Sun ◽  
Lei Yin ◽  
Fei Tang ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Disease Progression ◽  
Hepatic Steatosis ◽  
Proinflammatory Cytokines ◽  
Myeloid Cell ◽  
Metabolic Inflammation ◽  
Molecular Patterns ◽  
Specific Deletion

Myeloid cells, particularly macrophages, mediate metabolic inflammation, thus promoting insulin resistance and metabolic disease progression in obesity. Numerous cytokines, toxic metabolites, damage-associated molecular patterns, and pathogen-associated molecular patterns are involved in activating macrophages via their cognate receptors in obesity. TRAF3 (TNF receptor-associated factor 3) is a common signaling molecule for these ligands/receptors and negatively regulates the proinflammatory NF-κB and MAPK pathways, but its metabolic activity is unknown. We here show that myeloid cell TRAF3 is required for metabolic inflammation and metabolic disease progression in obesity. Myeloid cell-specific deletion of TRAF3 significantly attenuated insulin resistance, hyperglycemia, hyperinsulinemia, glucose intolerance, and hepatic steatosis in mice with either genetic ( ob/ob) or high-fat diet (HFD)-induced obesity. Myeloid cell-specific deletion of TRAF3 had the opposite effects on metabolic inflammation between obese and lean mice. It decreased the expression of proinflammatory cytokines in the liver and adipose tissue of obese mice and largely prevented HFD-induced inflammation in these metabolic tissues; by contrast, in lean mice, it increased the expression of proinflammatory cytokines in the liver and adipose tissue. These data suggest that, in obesity progression, myeloid TRAF3 functionally switches its activity from anti-inflammatory to proinflammatory modes, thereby coupling overnutrition to metabolic inflammation, insulin resistance, and metabolic disease.

scholarly journals Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

Science ◽  
2019 ◽  
Vol 365 (6451) ◽  
pp. 386-392 ◽  
Author(s):  
Bhagirath Chaurasia ◽  
Trevor S. Tippetts ◽  
Rafael Mayoral Monibas ◽  
Jinqi Liu ◽  
Ying Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Double Bond ◽  
Hepatic Steatosis ◽  
Metabolic Disorders ◽  
Glucose Utilization ◽  
Lipid Uptake ◽  
Dihydroceramide Desaturase ◽  
Dihydroceramide Desaturase 1 ◽  
And Storage ◽  
Specific Deletion

Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.

scholarly journals INSIGHTS INTO THE ROLE OF MORUS ALBA IN REVERSING OBESITY-ASSOCIATED HEPATIC STEATOSIS AND RELATED METABOLIC DISORDER IN RATS

2016 ◽  
pp. 231
Author(s):  
Hanaa H. Ahmed ◽  
Fatehya M Metwally ◽  
Hend Rashad ◽  
Asmaa M Zaazaa
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Metabolic Disorder ◽  
Ethanolic Extract ◽  
Treated Group ◽  
Morus Alba ◽  
The Other ◽  
Obese Group ◽  
Control Group

<p>ABSTRACT<br />Objective: The goal of the present study was to examine the viability of Morus alba (M. alba) ethanolic extract in repression of obesity-associated<br />hepatic steatosis and related metabolic disorder; dyslipidemia, hyperinsulinemia, and glycemic status.<br />Methods: Adult female albino rats were randomly assigned into four groups, eight rats each as follows: Group (1) control group received standard<br />rodent diet for 24 weeks. The other three groups administered high cholesterol diet for 12 weeks and served as obese group, M. alba-treated group,<br />and simvastatin-treated group.<br />Results: The current results showed an increment in thoracic circumference (TCX) and abdominal circumferences (AC) as well as body mass index<br />(BMI) in obese group. In addition, dyslipidemia, hyperinsulinemia, hyperglycemia, and insulin resistance have been elucidated in obese group.<br />Moreover, hepatic malondialdehyde (MDA), nitric oxide (NO), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin<br />values were significantly increased in obese groups versus control group. On the other hand, administration of ethanolic extract of Morus alba or<br />simvastatin could significantly lessen BMI and in addition to improve dyslipidemia in obese group. Glucose, insulin levels, and insulin resistance value<br />in serum samples demonstrated a significant reduction in obese group upon treatment with M. alba ethanolic extract or simvastatin. Furthermore,<br />noticeable depletion in hepatic MDA, NO contents, serum ALT, AST activities, and serum bilirubin level was recorded as a result of treatment with<br />either ethanolic extract of M. alba or simvastatin. Histopathological examination of liver tissue showed ballooning degeneration in the hepatocytes<br />(hepatic steatosis) associated with inflammatory cells penetration in portal zone in obese group. Meanwhile, the treatment of obese groups with<br />ethanolic extract of M. alba or simvastatin was found to restore the structural organization of the liver.<br />Conclusion: The present findings provide a novel aspect for understanding of the role of M. alba against obesity-associated liver diseases and related<br />metabolic disorder. The mechanisms underlying these effects seem to depend on the hypolipidemic potential, anti-inflammatory property, and<br />antioxidant activity of its phytochemicals.<br />Keywords: Obesity, Morus alba, Dyslipidemia, Hyperinsulinemia, Hyperglycemia, Hepatic steatosis.</p>

scholarly journals Ethnic differences in hepatic steatosis: An insulin resistance paradox?

Hepatology ◽  
2008 ◽  
Vol 49 (3) ◽  
pp. 791-801 ◽  
Author(s):  
Richard Guerrero ◽  
Gloria L. Vega ◽  
Scott M. Grundy ◽  
Jeffrey D. Browning
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Ethnic Differences

scholarly journals Aberrant Hepatic Expression of PPARγ2 Stimulates Hepatic Lipogenesis in a Mouse Model of Obesity, Insulin Resistance, Dyslipidemia, and Hepatic Steatosis

2006 ◽  
Vol 281 (49) ◽  
pp. 37603-37615 ◽  
Author(s):  
Yuan-Li Zhang ◽  
Antonio Hernandez-Ono ◽  
Patty Siri ◽  
Stuart Weisberg ◽  
Donna Conlon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Hepatic Steatosis ◽  
Hepatic Lipogenesis ◽  
Hepatic Expression

Therapeutic potential of curcumin in non-alcoholic steatohepatitis

2005 ◽  
Vol 18 (2) ◽  
pp. 212-221 ◽  
Author(s):  
Haim Shapiro ◽  
Rafael Bruck
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Animal Studies ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Indirect Evidence ◽  
Deficient Diet ◽  
Alcoholic Steatohepatitis ◽  
Ppar Γ

Non-alcoholic steatohepatitis (NASH) may be associated with a number of clinical conditions, but it occurs most commonly in patients with insulin resistance. There is as yet no established disease-modifying treatment, and a safe and broadly available agent that targets hepatic steatosis, insulin resistance, inflammation and fibrosis is necessary. The polyphenolic compound curcumin exhibits antioxidant and anti-inflammatory properties, inhibits NF-κB and activates PPAR-γ. In rodents, curcumin prevents dietary-induced hepatic steatosis, hepatic stellate cell activation and production of fibrotic proteins, and ameliorates steatohepatitis induced by the intake of alcohol or a methionine–choline-deficient diet. Indirect evidence suggests that curcumin may improve insulin sensitivity in diabetes and inflammatory states. The present paper reviews the numerous cellular and animal studies indicating that curcumin attenuates many of the pathophysiological processes involved in the development and progression of NASH. It is suggested that basic and clinical studies on curcumin in the development and progression of NASH are indicated.

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

Edible Red Seaweed Campylaephora Hypnaeoides J. Agardh Alleviates Obesity and Related Metabolic Disorders in Mice by Suppressing Oxidative Stress and Inflammatory Response

2021 ◽  
Author(s):  
Shigeru Murakami ◽  
Chihiro Hirazawa ◽  
Rina Yoshikawa ◽  
Toshiki Mizutani ◽  
Takuma Ohya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
White Adipose Tissue ◽  
Metabolic Disorders ◽  
Public Health Problem ◽  
Serum Levels ◽  
Diet Group ◽  
Raw264.7 Cells ◽  
Edible Seaweed

Abstract Background: The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice.Methods: Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells. Results: Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, diabetes, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor a (TNF-a), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-a, and interleukin-6 (IL-6) levels, while it decreased glutathione (GSH) and superoxide dismutase (SOD). These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-a in macrophage RAW264.7 cells. Conclusions: The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, diabetes, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides.

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