Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects

Yore, Mark M.; Syed, Ismail; Moraes‐Vieira, Pedro M.; Zhang, Tejia; Herman, Mark A.; Homan, Edwin A.; Patel, Rajesh; Lee, Jennifer; Chen, Shili; Peroni, Odile D.; Dhaneshwar, Abha S.; Hammarstedt, Ann; Smith, Ulf; McGraw, Timothy E.; Saghatelian, Alan; Kahn, Barbara B.

doi:10.1016/j.cell.2014.09.035

Cited by 650 publications

(1,219 citation statements)

References 38 publications

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“…The recent observation of selective insulin resistance in certain conditions (14,16,17,49) has added to the complexity of this phenomenon. In view of the central role of the adipocyte in whole body insulin sensitivity (18,50), in the present study, we have analyzed the selectivity of insulin resistance in various adipose models. Impaired glucose metabolism was a unifying feature of all insulin resistance models, whereas other processes such as lipolysis and protein synthesis were generally not impaired.…”

Section: Discussionmentioning

confidence: 99%

Selective Insulin Resistance in Adipocytes

Tan

Fisher‐Wellman

Fazakerley³

et al. 2015

Journal of Biological Chemistry

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Background: Insulin resistance is an early risk factor for metabolic disease. Results: Using various insulin resistance models, insulin regulation of glucose metabolism was universally blunted, whereas other actions (protein synthesis and anti-lipolysis) were unimpaired. Conclusion: Insulin resistance is selective for glucose metabolism in adipocytes. Significance: Chronic hyperactivation of unaffected insulin action pathways in the context of the metabolic syndrome likely contributes to disease progression.

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Section: Discussionmentioning

confidence: 99%

Selective Insulin Resistance in Adipocytes

Tan

Fisher‐Wellman

Fazakerley³

et al. 2015

Journal of Biological Chemistry

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“…Other classes of lipids (e.g. the newly described fatty acid esters of hydroxy fatty acids [39]), remain to be tested.…”

Section: Catalytic Activitymentioning

confidence: 99%

Carnitine palmitoyltransferase 1C: From cognition to cancer

Casals

Zammit

Herrero

et al. 2016

Progress in Lipid Research

102

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Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression.Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with L-carnitine and acyl-CoA esters. The lack of an easily measurable biological activity has hampered attempts to elucidate the cellular and physiological role of CPT1C but has not diminished the interest of the biomedical research community in this CPT1 isoform. The observations that CPT1C binds malonyl-CoA and long-chain acyl-CoA suggest that it is a sensor of lipid metabolism in neurons, where it appears to impact ceramide and triacylglycerol (TAG) metabolism.CPT1C global knock-out mice show a wide range of brain disorders, including impaired cognition and spatial learning, motor deficits, and a deregulation in food intake and energy homeostasis. The first disease-causing CPT1C mutation was recently described in humans, with Cpt1c being identified as the gene causing hereditary spastic paraplegia. The putative role of CPT1C in the regulation of complex-lipid metabolism is supported by the observation that it is highly expressed in certain virulent tumor cells, conferring them resistance to glucose-and oxygen-deprivation. Therefore, CPT1C may be a promising target in the treatment of cancer. Here we review the molecular, biochemical, and structural properties of CPT1C and discuss its potential roles in brain function, and cancer.

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“…It has been recently shown that both DHA and ETA are anti‐inflammatory, and act through the free fatty acid receptor 4 (FFAR4) [Yore et al, 2014]. Therefore, it is likely that on the second day after BMP2 induction, since there is a decline in DHA, this period is inflammatory, but only on day 4, with an increase in EPA, does one, therefore, see a decline in initial inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

Davis

Salisbury

Olmsted-Davis

et al. 2015

J of Cellular Biochemistry

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Heterotopic ossification (HO) is the de novo formation of bone that occurs in soft tissue, through recruitment, expansion, and differentiation of multiple cells types including transient brown adipocytes, osteoblasts, chondrocytes, mast cells, and platelets to name a few. Much evidence is accumulating that suggests changes in metabolism may be required to accomplish this bone formation. Recent work using a mouse model of heterotopic bone formation reliant on delivery of adenovirus‐transduced cells expressing low levels of BMP2 showed the immediate expansion of a unique brown adipocyte‐like cell. These cells are undergoing robust uncoupled oxidative phosphorylation to a level such that oxygen in the microenvironment is dramatically lowered creating areas of hypoxia. It is unclear how these oxygen changes ultimately affect metabolism and bone formation. To identify the processes and changes occurring over the course of bone formation, HO was established in the mice, and tissues isolated at early and late times were subjected to a global metabolomic screen. Results show that there are significant changes in both glucose levels, as well as TCA cycle intermediates. Additionally, metabolites necessary for oxidation of stored lipids were also found to be significantly elevated. The complete results of this screen are presented here, and provide a unique picture of the metabolic changes occurring during heterotopic bone formation. J. Cell. Biochem. 117: 1044–1053, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

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Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects

Cited by 650 publications

References 38 publications

Selective Insulin Resistance in Adipocytes

Selective Insulin Resistance in Adipocytes

Carnitine palmitoyltransferase 1C: From cognition to cancer

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

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