Haw pectin pentaglaracturonide inhibits fatty acid synthesis and improves insulin sensitivity in high-fat-fed mice

2017 ◽  
Vol 34 ◽  
pp. 440-446 ◽  
Author(s):  
Suhong Li ◽  
Zhu Huang ◽  
Yinping Dong ◽  
Rugang Zhu ◽  
Tuoping Li
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
High Fat

scholarly journals Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

2016 ◽  
Vol 113 (13) ◽  
pp. E1796-E1805 ◽  
Author(s):  
Geraldine Harriman ◽  
Jeremy Greenwood ◽  
Sathesh Bhat ◽  
Xinyi Huang ◽  
Ruiying Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
Fatty Liver Disease ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase

Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein–protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.

Translational control by mTOR-independent routes: how eIF6 organizes metabolism

2016 ◽  
Vol 44 (6) ◽  
pp. 1667-1673 ◽  
Author(s):  
Annarita Miluzio ◽  
Sara Ricciardi ◽  
Nicola Manfrini ◽  
Roberta Alfieri ◽  
Stefania Oliveto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Synthesis ◽  
Translational Control ◽  
Metabolic Diseases ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Translational Machinery

Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types. Data on mice models have demonstrated that eIF6 cytoplasmic activity is rate-limiting for Myc-induced lymphomagenesis. In spite of this, eIF6 is neither transcriptionally regulated by Myc, nor post-transcriptionally regulated by mTOR. eIF6 stimulates a glycolytic and fatty acid synthesis program necessary for tumor growth. eIF6 increases the translation of transcription factors necessary for lipogenesis, such as CEBP/β, ATF4 and CEBP/δ. Insulin stimulation leads to an increase in translation and fat synthesis blunted by eIF6 deficiency. Paradoxycally, long-term inhibition of eIF6 activity increases insulin sensitivity, suggesting that the translational activation observed upon insulin and growth factors stimulation acts as a feed-forward mechanism regulating lipid synthesis. The data on the role that eIF6 plays in cancer and in insulin sensitivity make it a tempting pharmacological target for cancers and metabolic diseases. We speculate that eIF6 inhibition will be particularly effective especially when mTOR sensitivity to rapamycin is abrogated by RAS mutations.

scholarly journals Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing-Na Deng ◽  
Juan Li ◽  
Hong-Na Mu ◽  
Yu-Ying Liu ◽  
Ming-Xia Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
High Fat ◽  
The Metabolic Syndrome

This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC.

scholarly journals The effect of dietary fat on lipogenesis in mammary gland and liver from lactating and virgin mice

1969 ◽  
Vol 115 (4) ◽  
pp. 807-815 ◽  
Author(s):  
Stuart Smith ◽  
Harriet T. Gagné ◽  
Dorothy R. Pitelka ◽  
S. Abraham
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Corn Oil ◽  
Acid Synthesis ◽  
High Fat ◽  
C3h Mice ◽  
Parenchymal Cells

1. Virgin and lactating C3H mice maintained on laboratory chow were transferred to a high-fat (15% corn oil) or a fat-free diet 3 days before being killed. 2. The linoleate content of liver, mammary gland and milk was decreased in lactating mice given the fat-free diet but was increased in those fed on the high-fat diet. Changes in linoleate content and mammary gland followed a similar but much less marked trend in virgin animals. 3. Hepatic fatty acid synthesis in lactating and virgin mice fed on the fat-free diet was higher than in corresponding animals fed on either the chow or the high-fat diet. The lipogenic capacity of livers from mice fed on either the chow or the high-fat diet was greater in lactating than in virgin animals. These changes in hepatic lipogenic capacity were accompanied by alterations in the specific activities of certain enzymes involved in fat synthesis. 4. Mammary gland from virgin and lactating animals showed no such adaptation to dietary fat. Results indicate that fatty acid synthesis in neither mammary-gland parenchymal cells nor mammary-gland adipose cells can be influenced by dietary fat in the same way as in the hepatocyte.

Mode of action of choline. IV. Activity of the enzymes related to fatty acid synthesis and the levels of metabolic intermediates in choline-deficient rats

1969 ◽  
Vol 47 (10) ◽  
pp. 917-926 ◽  
Author(s):  
A. Chalvardjian
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Adenine Nucleotides ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
High Fat ◽  
Metabolic Intermediates ◽  
Fatty Livers ◽  
The Mean ◽  
Fat Diets

Three groups of choline-deficient (c.d.) and choline-supplemented (c.s.) rats were fed, respectively, a fat-free, a moderate (7%), or a high-fat (31.5%) diet for 3 days. Further groups of c.d. and c.s. rats on the 7% fat diet were killed at intervals of 2, 3, 4, 5, 8, 11, and 15 days. (1) The c.d. rats on the 7% and 31.5% fat diets developed fatty livers. (2) The activities in the liver of the enzymes related to lipogenesis were increased slightly in the initial stages in c.d. rats fed the 7% fat diet over their c.s. controls; but, by the end of 15 days the mean activities of the enyzmes were greater in the c.s. controls, indicating a diminished response of the c.d. livers to dietary challenges. (3) The hepatic levels of total adenine nucleotides and ATP were lower in the c.d. than in the c.s. rats fed the 7% and 31.5% fat diets. Increasing the levels of adenine nucleotides and ATP by feeding adenine sulfate did not prevent fatty liver in the c.d. rats fed a 7% fat diet. (4) Fatty acid oxidation, as assessed indirectly by the cytoplasmic NADH/NAD ratios and levels of β-hydroxybutyrate, was not impaired in the c.d. rats compared to the c.s. controls on diets containing 7% and 31.5% fat.

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