The central role performed by billions of vital central nervous system (CNS) lipids &#x201c;lipidomics&#x201d; in medical physiology is usually overlooked.  A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

Thomas Tallberg

Jan Dabek

Raija Hallamaa

Faik Atroshi

Lipidomics: The Function of Vital Lipids in Embryogenesis Preventing Autism Spectrum Disorders, Treating Sterile Inflammatory Diatheses with a Lymphopoietic Central Nervous System Component

Because of the failure of single modality approaches, combination therapy for cancer treatment is a promising alternative.  Sphingolipid analogs, with or without anticancer drugs, can improve tumor response. C16-pyridinium ceramide analog LCL30, was used in combination with photodynamic therapy (PDT), an anticancer treatment modality, to test the hypothesis that the combined treatment will trigger changes in the sphingolipid profile and promote cell death. Using SCCVII mouse squamous carcinoma cells, and the silicone phthalocyanine Pc 4 for PDT, we showed that combining PDT with LCL30 (PDT/LCL30) was more effective than individual treatments in raising global ceramide levels, as well as in reducing dihydrosphingosine levels. Unlike LCL30, PDT, alone or combined, increased total dihydroceramide levels. Sphingosine levels were unaffected by LCL30, but were abolished after PDT or the combination.  LCL30-triggered rise in sphingosine-1-phosphate was reversed post-PDT or the combination. DEVDase activation was evoked after PDT or LCL30, and was promoted post- PDT/LCL30. Neither mitochondrial depolarization nor apoptosis were observed after any of the treatments. Notably, treatment with the combination resulted in augmented overall cell killing. Our data demonstrate that treatment with PDT/LCL30 leads to enhanced global ceramide levels and DEVDase activation in the absence of apoptosis, and promotion of total cell killing.

Duska Separovic

Ziad H. Saad

Ethan A. Edwin

Jacek Bielawski

Jason S. Pierce

Eric Van Buren

Alicja Bielawska

C16-Ceramide Analog Combined with Pc 4 Photodynamic Therapy Evokes Enhanced Total Ceramide Accumulation, Promotion of DEVDase Activation in the Absence of Apoptosis, and Augmented Overall Cell Killing

The lipid-signalling molecule ceramide is known to induce apoptosis in a variety of cell types. Inhibition of the lysosomal acid ceramidase can increase cellular ceramide levels and thus induce apoptosis. Indeed, inhibitors of acid ceramidase have been reported to induce cell death and to display potentiating effects to classical radio- or chemo therapy in a number of <i  >in vitro</i> and <i  >in vivo</i> cancer models. The most potent <i  >in vitro</i> inhibitor of acid ceramidase, B-13, recently revealed to be virtually inactive towards lysosomal acid ceramidase in living cells. In contrast, a number of weakly basic B-13 analogues have been shown to accumulate in the acidic compartments of living cells and to efficiently inhibit lysosomal acid ceramidase. However, introduction of weakly basic groups at the <i  >&#x3c9;</i>-position of the fatty acid moiety of B-13 led to a significant reduction of potency towards acid ceramidase from cellular extracts. Herein, we report a novel B-13-derived scaffold for more effective inhibitors of acid ceramidase. Furthermore, we provide hints for an introduction of basic functional groups at an alternative site of the B-13 scaffold that do not interfere with acid ceramidase inhibition <i  >in vitro</i>.

Denny Proksch

Jan Jasper Klein

Christoph Arenz

Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues

Most mammalian sphingolipids contain a 4,5-(<i>E</i>)-double bond. We report on the chemical synthesis of a dihydroceramide derivative that prevents the introduction of the double bond into sphingolipids. Minimal alteration of the parent structure by formally replacing the hydrogen atoms in the 5- and in the 6-position of the sphinganine backbone by a methylene group leads to an inhibitor of dihydroceramide desaturase in cultured cells. In the presence of 10&#8211;50 &#x03BC;M of compound (<b>1</b>), levels of biosynthetically formed dihydroceramide and&#8212;surprisingly&#8212;also of phytoceramide are elevated at the expense of ceramide. The cells respond to the lack of unsaturated sphingolipids by an elevation of mRNAs of enzymes required for sphingosine formation. At the same time, the analysis of proliferation and differentiation markers indicates that the sphingolipid double bond is required to keep the cells in a differentiated state.

Susanne Brodesser

Thomas Kolter

Dihydroceramide Desaturase Inhibition by a Cyclopropanated Dihydroceramide Analog in Cultured Keratinocytes

This paper explores the way ceramide, sphingosine, ceramide 1-phosphate, and sphingosine 1-phosphate modulate the generation of second lipid messengers from phosphatidic acid in two experimental models of the central nervous system: in vertebrate rod outer segments prepared from dark-adapted retinas as well as in rod outer segments prepared from light-adapted retinas  and in rat cerebral cortex synaptosomes under physiological aging conditions. Particular attention is paid to lipid phosphate phosphatase, diacylglycerol lipase, and monoacylglycerol lipase. Based on the findings reported in this paper, it can be concluded that proteins related to phototransduction phenomena are involved in the effects derived from sphingosine 1-phosphate/sphingosine or ceramide 1-phosphate/ceramide and that age-related changes occur in the metabolism of phosphatidic acid from cerebral cortex synaptosomes in the presence of either sphingosine 1-phosphate/sphingosine or ceramide 1-phosphate/ceramide. The present paper demonstrates, in two different models of central nervous system, how sphingolipids influence phosphatidic acid metabolism under different physiological conditions such as light and aging.

Susana J. Pasquar&#233;

Virginia L. Gaveglio

Norma M. Giusto

Regulation of Phosphatidic Acid Metabolism by  Sphingolipids in the Central Nervous System

Recent studies indicate that significant health benefits involving the regulation of signaling proteins result from the consumption of omega-3 polyunsaturated fatty acids (<svg     style="vertical-align:-0.1638pt;width:10.975px;" id="M2" height="8.0500002" version="1.1" viewBox="0 0 10.975 8.0500002" width="10.975"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>-3 PUFAs).  Serum response factor (SRF) is involved in transcriptional regulation of muscle growth and differentiation.  SRF levels are increased in the aging heart muscle. It has not been examined whether SRF is made by adipocytes and whether SRF secretion by adipocytes is modulated by PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M3" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> agonist DHA. 
Adiponectin is made exclusively by adipocytes.  We and others have previously reported that PUFAs such as DHA increase adiponectin levels and secretion in adipocytes.  Here we show that DHA downregulates SRF with a simultaneous upregulation of adiponectin and that both these responses are reversible by PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M4" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> antagonist.  Furthermore, there appears to be a direct relationship between DHA exposure and increased levels of membrane-associated high-density adiponectin, as well as lower levels of membrane-associated SRF. Thus, we find that the levels of SRF and adiponectin are inversely related in response to treatment with PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M5" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> agonist DHA. Decreased levels of SRF along with increase in membrane-associated adiponectin could in part mediate the health benefits of DHA. 


Clayton Johnson

Roslyn Williams

Jeanne Y. Wei

Gouri Ranganathan

Regulation of Serum Response Factor and Adiponectin by  PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5
t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z"/></g></svg> Agonist Docosahexaenoic Acid

The addition of polyoxyethylene sorbitan monooleate (Tween 80) to a culture of mycobacteria greatly influences cell permeability and sensitivity to antibiotics but very little is known regarding the underlying mechanism.  Here we show that <i  >Corynebacterium matruchotii</i> (surrogate of mycobacteria) converts Tween 80 to a structural series of polyoxyethylenic acids which are then used to form novel series-2A and series-2B glycolipids.  Minor series-3 glycolipids were also synthesized.  The polyoxyethylenic acids replaced corynomycolic acids in the cell wall.  Correspondingly the trehalose dicorynomycolate content was reduced.  MALDI mass spectrometry, MS-MS, <svg     style="vertical-align:-0.0pt;width:19.475px;" id="M1" height="15.8375" version="1.1" viewBox="0 0 19.475 15.8375" width="19.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>-NMR, and <svg     style="vertical-align:-0.20473pt;width:23.475px;" id="M2" height="16.1" version="1.1" viewBox="0 0 23.475 16.1" width="23.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>-NMR were used to characterize the series-2 glycolipids. Series-2A glycolipid is trehalose 6-<svg     style="vertical-align:-3.3907pt;width:33.162498px;" id="M3" height="15.65" version="1.1" viewBox="0 0 33.162498 15.65" width="33.162498"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.362)"><use xlink:href="#x43"/></g>

			<g transform="matrix(.012,-0,0,-.012,11.363,15.45)"><use xlink:href="#x33"/></g><g transform="matrix(.012,-0,0,-.012,17.074,15.45)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g><g transform="matrix(.012,-0,0,-.012,22.785,15.45)"><path id="x2236" d="M223 355q0 -25 -15.5 -41.5t-39.5 -16.5t-40 16.5t-16 41.5t16 41t40 16t39.5 -16t15.5 -41zM223 46q0 -26 -16 -42t-40 -16t-39.5 16t-15.5 42q0 24 16 40.5t39 16.5q24 0 40 -16.5t16 -40.5z" /></g><g transform="matrix(.012,-0,0,-.012,26.759,15.45)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g>

		
	
</svg>-corynomycolate-<svg     style="vertical-align:-0.1638pt;width:12.4375px;" id="M4" height="17.9125" version="1.1" viewBox="0 0 12.4375 17.9125" width="12.4375"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,17.65)"><use xlink:href="#x36"/></g>

			<g transform="matrix(.012,-0,0,-.012,8.225,9.488)"><path id="x2032" d="M227 744l-123 -338l-31 15l73 368q12 3 41.5 -8t36.5 -20z" /></g>

		
	
</svg>-polyoxyethylenate and series-2B glycolipid is trehalose 6-<svg     style="vertical-align:-3.3907pt;width:33.162498px;" id="M5" height="15.65" version="1.1" viewBox="0 0 33.162498 15.65" width="33.162498"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.362)"><use xlink:href="#x43"/></g>

			<g transform="matrix(.012,-0,0,-.012,11.363,15.45)"><use xlink:href="#x33"/></g><g transform="matrix(.012,-0,0,-.012,17.074,15.45)"><use xlink:href="#x36"/></g><g transform="matrix(.012,-0,0,-.012,22.785,15.45)"><use xlink:href="#x2236"/></g><g transform="matrix(.012,-0,0,-.012,26.759,15.45)"><use xlink:href="#x32"/></g>

		
	
</svg>-corynomycolate-<svg     style="vertical-align:-0.1638pt;width:12.4375px;" id="M6" height="17.9125" version="1.1" viewBox="0 0 12.4375 17.9125" width="12.4375"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,17.65)"><use xlink:href="#x36"/></g>

			<g transform="matrix(.012,-0,0,-.012,8.225,9.488)"><use xlink:href="#x2032"/></g>

		
	
</svg>-furan ring-containing polyoxyethylenate. <i  >Mycobacterium smegmatis</i> grown in the presence of Tween 80 also synthesizes series-2 type glycolipids. The synthesis of these novel glycolipids in corynebacteria and mycobacteria should result in gross changes in the cell wall permeability and drug sensitivity.

Cindy Wang

Engy A. Mahrous

Richard E. Lee

Martha M. Vestling

Kuni Takayama

Novel Polyoxyethylene-Containing Glycolipids Are  Synthesized in <i>Corynebacterium matruchotii</i> and <i>Mycobacterium smegmatis</i> Cultured in the Presence of Tween 80

About this journal

<p><em>Journal of Lipids</em> provides a forum for scientists, physicians, and nutritionists working in all aspects of lipids research. Topics covered include their biochemistry, synthesis, function in health and disease, and nutrition.</p>


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title

Journal of Lipids provides a forum for scientists, physicians, and nutritionists working in all aspects of lipids research. Topics covered include their biochemistry, synthesis, function in health and disease, and nutrition.

Journal of Lipids