Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease

Diraison, Frédérique; Moulin, P.; Beylot, M.

doi:10.1016/s1262-3636(07)70061-7

Cited by 362 publications

(257 citation statements)

References 37 publications

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“…XBP1s Reduces Hepatic Diacylglycerol Levels and Inhibits PKC⑀ Translocation-TG in the liver are primarily formed through esterification of fatty acids (25). Diacylglycerol (DAG), which consists of a glycerol backbone with two fatty acyl groups, is an intermediate of the TG synthetic pathway and a TG precursor molecule.…”

Section: Xbp1smentioning

confidence: 99%

XBP1s Is an Anti-lipogenic Protein

Herrema

Zhou

Zhang

et al. 2016

Journal of Biological Chemistry

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Endoplasmic reticulum (ER) stress has been shown to contribute to various metabolic diseases, including non-alcoholic fatty liver disease and type 2 diabetes. Reduction of ER stress by treatment with chemical chaperones or overexpression of ER chaperone proteins alleviates hepatic steatosis. Nonetheless, X-box binding protein 1s (XBP1s), a key transcription factor that reduces ER stress, has been proposed as a lipogenic transcription factor. In this report, we document that XBP1s leads to suppression of lipogenic gene expression and reduction of hepatic triglyceride and diacylglycerol content in livers of dietinduced obese and genetically obese and insulin-resistant ob/ob mice. Furthermore, we also show that PKC⑀ activity, which correlates with fatty liver and which causes insulin resistance, was significantly reduced in diet-induced obese mice. Finally, we have shown that XBP1s reduces the hepatic fatty acid synthesis rate and enhances macrolipophagy, an initiating step in lipolysis. Our results reveal that XBP1s reduces hepatic lipogenic gene expression and improves hepatosteatosis in mouse models of obesity and insulin resistance, which leads us to conclude that XBP1s has anti-lipogenic properties in the liver.

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Section: Xbp1smentioning

confidence: 99%

XBP1s Is an Anti-lipogenic Protein

Herrema

Zhou

Zhang

et al. 2016

Journal of Biological Chemistry

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“…Thus, patients are exposed to the dual threats of poorly controlled glycemia and unchecked lipogenesis, with the latter contributing to non-alcoholic fatty liver disease and atherogenic dyslipidemia (3)(4)(5). Although the pathophysiology of selective IR remains unclear, it is generally acknowledged that the pathways to insulin regulation of glucose versus triglyceride production diverge downstream of Akt (6).…”

mentioning

confidence: 99%

Pathogenesis of Selective Insulin Resistance in Isolated Hepatocytes

Cook

Langlet

Kido

et al. 2015

Journal of Biological Chemistry

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Background:The liver produces both excessive glucose and lipids in type 2 diabetes. Results: Glucose production is more vulnerable to insulin receptor (InsR) impairment ex vivo than is lipogenesis. Conclusion: Selective insulin resistance arises due to inherent, cell-autonomous differences in the insulin responsiveness of glucose versus lipid metabolism. Significance: InsR itself may represent a locus of treatment of diabetes.

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“…Non-alcoholic fatty liver disease (NAFLD), 2 which refers to a disease spectrum ranging from simple triglyceride accumulation (hepatic steatosis) to hepatic steatohepatitis (steatosis with inflammation), fibrosis, and cirrhosis, has become the most frequent etiological factor of chronic liver diseases (1).…”

Section: Hepatic Steatosis Characterized By Ectopic Hepatic Triglycementioning

confidence: 99%

“…De novo lipogenesis is markedly increased in NAFLD patients compared with healthy subjects, contributing to the excessive TG deposition in the liver (2). Moreover, hepatic lipogenesis, which is normally inhibited under fasting conditions, is relatively high in the fasted state and fails to further increase in the postprandial periods in NAFLD patients (3).…”

Section: Hepatic Steatosis Characterized By Ectopic Hepatic Triglycementioning

confidence: 99%