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Journal ArticleDOI

De novo lipogenesis in health and disease.

TLDR
Therapeutic targeting of this pathway may open a new window of opportunity for combating various lipogenesis-driven pathological conditions - including obesity, cancer and certain viral infections.
Abstract
Background De novo lipogenesis (DNL) is a complex and highly regulated metabolic pathway. In normal conditions DNL converts excess carbohydrate into fatty acids that are then esterified to storage triacylglycerols (TGs). These TGs could later provide energy via β-oxidation. In human body this pathway is primarily active in liver and adipose tissue. However, it is considered to be a minor contributor to the serum lipid homeostasis. Deregulations in the lipogenic pathway are associated with diverse pathological conditions. Scope of review The present review focuses on our current understanding of the lipogenic pathway with special reference to the causes and consequences of aberrant DNL. Major conclusions The deregulation of DNL in the major lipogenic tissues of the human body is often observed in various metabolic anomalies — including obesity, non-alcoholic fatty liver disease and metabolic syndrome. In addition to that de novo lipogenesis is reported to be exacerbated in cancer tissues, virus infected cells etc. These observations suggest that inhibitors of the DNL pathway might serve as therapeutically significant compounds. The effectiveness of these inhibitors in treatment of cancer and obesity has been suggested by previous works. General significance De novo lipogenesis – which is an intricate and highly regulated pathway – can lead to adverse metabolic consequences when deregulated. Therapeutic targeting of this pathway may open a new window of opportunity for combating various lipogenesis-driven pathological conditions — including obesity, cancer and certain viral infections.

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Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

TL;DR: Evidence is provided that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle, and recent advances in the understanding of how Steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication are discussed.
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Mechanisms and consequences of intestinal dysbiosis

TL;DR: The characterization of the changes leading to intestinal dysbiosis and the identification of the microbial taxa contributing to pathological effects are essential prerequisites to better understand the impact of the microbiota on health and disease.
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New insights into the pathophysiology of dyslipidemia in type 2 diabetes

TL;DR: Recent advances in the understanding of the pathophysiology of diabetic dyslipidemia are reviewed, showing that triglyceride-rich lipoproteins and their remnants are atherogenic.
Journal ArticleDOI

De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose.

TL;DR: Whether DNL plays a significant role in the pathogenesis of insulin resistance is yet to be fully elucidated, but it may be that the prevalent products of this synthetic process induce some aspect of hepatic insulin resistance.
Journal ArticleDOI

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

TL;DR: The aim of this review is to summarize the current knowledge addressing the antidiabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes, tyrosine kinase inhibitor, AMPK, PPAR, and NF-κB.
References
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Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.

TL;DR: In this article, the authors quantified the biological sources of hepatic and plasma lipoprotein TAG in NAFLD patients, using stable isotopes for four days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipid TAG.
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Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis

TL;DR: FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.
Journal ArticleDOI

Nonalcoholic fatty liver disease

TL;DR: The etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management are discussed in this paper, where the authors discuss the etiology and pathogenesis of NFLD.
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