scholarly journals Extracellular Fatty Acid Synthase: A Possible Surrogate Biomarker of Insulin Resistance

Diabetes ◽  
2010 ◽  
Vol 59 (6) ◽  
pp. 1506-1511 ◽  
Author(s):  
J. M. Fernandez-Real ◽  
J. A. Menendez ◽  
J. M. Moreno-Navarrete ◽  
M. Bluher ◽  
A. Vazquez-Martin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Extracellular Fatty Acid

Serum concentrations of extracellular fatty acid synthase in patients with steatohepatitis

2009 ◽  
Vol 47 (9) ◽  
Author(s):  
Judit Marsillach ◽  
Cristina Oliveras-Ferraros ◽  
Raúl Beltrán ◽  
Anna Rull ◽  
Gerard Aragonès ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Serum Concentrations ◽  
Extracellular Fatty Acid

scholarly journals Correction: The Fatty Acid Synthase Inhibitor Platensimycin Improves Insulin Resistance without Inducing Liver Steatosis in Mice and Monkeys

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170721 ◽  
Author(s):  
Sheo B. Singh ◽  
Ling Kang ◽  
Andrea R. Nawrocki ◽  
Dan Zhou ◽  
Margaret Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Liver Steatosis ◽  
Synthase Inhibitor

scholarly journals Fatty Acid Synthase: Association with Insulin Resistance, Type 2 Diabetes, and Cancer

2009 ◽  
Vol 55 (3) ◽  
pp. 425-438 ◽  
Author(s):  
Javier A Menendez ◽  
Alejandro Vazquez-Martin ◽  
Francisco Jose Ortega ◽  
Jose Manuel Fernandez-Real
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
De Novo ◽  
Genetic Alterations ◽  
Insulin Resistant

Abstract Background: An emerging paradigm supports the notion that deregulation of fatty acid synthase (FASN)-catalyzed de novo FA biogenesis could play a central role in the pathogenesis of metabolic diseases sharing the hallmark of insulin-resistance. Content: We reviewed pharmacological and genetic alterations of FASN activity that have been shown to significantly influence energy expenditure rates, fat mass, insulin sensitivity, and cancer risk. This new paradigm proposes that insulin-resistant conditions such as obesity, type 2 diabetes, and cancer arise from a common FASN-driven “lipogenic state”. An important question then is whether the development or the progression of insulin-related metabolic disorders can be prevented or reversed by the modulation of FASN status. If we accept the paradigm of FASN dysfunction as a previously unrecognized link between insulin resistance, type 2 diabetes, and cancer, the use of insulin sensitizers in parallel with forthcoming FASN inhibitors should be a valuable therapeutic approach that, in association with lifestyle interventions, would concurrently improve energy-flux status, ameliorate insulin sensitivity, and alleviate the risk of lipogenic carcinomas. Conclusions: Although the picture is currently incomplete and researchers in the field have plenty of work ahead, the latest clinical and experimental evidence that we discuss illuminates a functional and drug-modifiable link that connects FASN-driven endogenous FA biosynthesis, insulin action, and glucose homeostasis in the natural history of insulin-resistant pathologies.

scholarly journals Dietary Complex and Slow Digestive Carbohydrates Prevent Fat Deposits During Catch-Up Growth in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2568
Author(s):  
Rafael Salto ◽  
María D Girón ◽  
Carolina Ortiz-Moral ◽  
Manuel Manzano ◽  
Jose D Vílchez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Recovery Period ◽  
Muscle Performance ◽  
Liver Fat ◽  
Fat Deposits ◽  
Catch Up ◽  
Metabolic Inflexibility

A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early caloric restriction: an increase in adiposity combined with poorer muscle performance, insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in myocyte enhancer factor 2D (MEF2D) and creatine kinase as markers of muscle differentiation as well as better insulin sensitivity, enhanced glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted glycogen storage and decreased fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as obesity, insulin resistance, dyslipidemia, and liver fat deposits later in life.

scholarly journals Prenatal and Postnatal Pathways to Obesity: Different Underlying Mechanisms, Different Metabolic Outcomes

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2345-2354 ◽  
Author(s):  
Nichola M. Thompson ◽  
Amy M. Norman ◽  
Shawn S. Donkin ◽  
Ravi R. Shankar ◽  
Mark H. Vickers ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Metabolic Regulation ◽  
Fatty Acid Synthase ◽  
Whole Body ◽  
High Fat ◽  
Metabolic Outcomes ◽  
Underlying Mechanisms ◽  
Pkc Ζ

Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C ζ (PKC ζ) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC ζ with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO.

scholarly journals The Fatty Acid Synthase Inhibitor Platensimycin Improves Insulin Resistance without Inducing Liver Steatosis in Mice and Monkeys

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164133 ◽  
Author(s):  
Sheo B. Singh ◽  
Ling Kang ◽  
Andrea R. Nawrocki ◽  
Dan Zhou ◽  
Margaret Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Liver Steatosis ◽  
Synthase Inhibitor

AMPK-sensed cellular energy state regulates the release of extracellular Fatty Acid Synthase

2009 ◽  
Vol 378 (3) ◽  
pp. 488-493 ◽  
Author(s):  
Cristina Oliveras-Ferraros ◽  
Alejandro Vazquez-Martin ◽  
Jose Manuel Fernández-Real ◽  
Javier A. Menendez
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Energy State ◽  
Cellular Energy ◽  
Extracellular Fatty Acid

scholarly journals Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance

2000 ◽  
Vol 83 (S1) ◽  
pp. S59-S66 ◽  
Author(s):  
Steven D. Clarke
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Balance ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Synthase ◽  
Uncoupling Protein ◽  
Dietary Factors ◽  
Acid Oxidation ◽  
Genes Encoding

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play essential roles in the maintenance of energy balance and glucose metabolism. The data discussed indicate that dietary PUFA function as fuel partitioners in that they direct glucose toward glycogen storage, and direct fatty acids away from triglyceride synthesis and assimilation and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to have the unique ability to enhance thermogenesis and thereby reduce the efficiency of body fat deposition. PUFA exert their effects on lipid metabolism and thermogenesis by up-regulating the transcription of the mitochondrial uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while simultaneously down-regulating the transcription of genes encoding proteins involved in lipid synthesis (e.g. fatty acid synthase). The potential transcriptional mechanism and the transcription factors affected by PUFA are discussed. Moreover, the data are interpreted in the context of the role that PUFA may play as dietary factors in the development of obesity and insulin resistance. Collectively the results of these studies suggest that the metabolic functions governed by PUFA should be considered as part of the criteria utilized in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the optimum dietary ratio for n-6 : n-3 fatty acids.

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