ELOVL3 Is an Important Component for Early Onset of Lipid Recruitment in Brown Adipose Tissue*

During the recruitment process of brown adipose tissue, the mRNA level of the fatty acyl chain elongase Elovl3 is elevated more than 200-fold in cold-stressed mice. We have obtained Elovl3-ablated mice and report here that, although cold-acclimated Elovl3-ablated mice experienced an increased heat loss due to impaired skin barrier, they were unable to hyperrecruit their brown adipose tissue. Instead, they used muscle shivering in order to maintain body temperature. Lack of Elovl3 resulted in a transient decrease in the capacity to elongate saturated fatty acyl-CoAs into very long chain fatty acids, concomitantly with the occurrence of reduced levels of arachidic acid (C20:0) and behenic acid (C22:0) in brown adipose tissue during the initial cold stress. This effect on very long chain fatty acid synthesis could be illustrated as a decrease in the condensation activity of the elongation enzyme. In addition, warm-acclimated Elovl3-ablated mice showed diminished ability to accumulate fat and reduced metabolic capacity within the brown fat cells. This points to ELOVL3 as an important regulator of endogenous synthesis of saturated very long chain fatty acids and triglyceride formation in brown adipose tissue during the early phase of the tissue recruitment.

[1]  N. Baumann,et al.  THE ACTIVITY OF PARTIAL REACTIONS IN THE CHAIN ELONGATION OF PALMITOYL‐CoA AND STEAROYL‐CoA BY MOUSE BRAIN MICROSOMES , 1979, Journal of neurochemistry.

[2]  T. Raclot Selective mobilization of fatty acids from adipose tissue triacylglycerols. , 2003, Progress in lipid research.

[3]  C. J. Lewis,et al.  Identification and expression of mammalian long-chain PUFA elongation enzymes , 2002, Lipids.

[4]  M. Glotzer,et al.  Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. , 1985, The Journal of biological chemistry.

[5]  Sidney Udenfriend,et al.  Fluorescamine: A Reagent for Assay of Amino Acids, Peptides, Proteins, and Primary Amines in the Picomole Range , 1972, Science.

[6]  B. Cannon,et al.  Respiratory and thermogenic capacities of cells and mitochondria from brown and white adipose tissue. , 2001, Methods in molecular biology.

[7]  M. Capecchi,et al.  Role for ELOVL3 and Fatty Acid Chain Length in Development of Hair and Skin Function* , 2004, Journal of Biological Chemistry.

[8]  C. Polnaszek,et al.  The fluidity and organization of mitochondrial membrane lipids of the brown adipose tissue of cold-adapted rats and hamsters as determined by nitroxide spin probes. , 1975, Archives of biochemistry and biophysics.

[9]  E. Saggerson,et al.  Effect of noradrenaline on triacylglycerol synthesis in rat brown adipocytes. , 1989, The Biochemical journal.

[10]  Stuart Smith The animal fatty acid synthase: one gene, one polypeptide, seven enzymes , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  A. Géloën,et al.  Beta-adrenergic stimulation of brown adipocyte proliferation. , 1988, The American journal of physiology.

[12]  K. Sato,et al.  Spontaneous sweat secretion in calcium-free strontium medium. , 1982, The American journal of physiology.

[13]  S. Enna Current protocols in pharmacology , 1998 .

[14]  Hitoshi Yamashita,et al.  Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese , 1997, nature.

[15]  P. Wertz,et al.  Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice. , 2003, The Journal of investigative dermatology.

[16]  B A Horwitz,et al.  Brown fat and thermogenesis. , 1969, Physiological reviews.

[17]  Jan Nedergaard,et al.  Brown adipose tissue: function and physiological significance. , 2004, Physiological reviews.

[18]  D. L. Cinti,et al.  Decreased Long‐Chain Fatty Acyl CoA Elongation Activity in Quaking and Jimpy Mouse Brain: Deficiency in One Enzyme or Multiple Enzyme Activities? , 1991, Journal of neurochemistry.

[19]  J. Warrington,et al.  Identification of a Mammalian Long Chain Fatty Acyl Elongase Regulated by Sterol Regulatory Element-binding Proteins* , 2001, The Journal of Biological Chemistry.

[20]  O. Suzuki,et al.  Identification and Expression of a Rat Fatty Acid Elongase Involved in the Biosynthesis of C18 Fatty Acids , 2002, Bioscience, biotechnology, and biochemistry.

[21]  L. Janský NON‐SHIVERING THERMOGENESIS AND ITS THERMOREGULATORY SIGNIFICANCE , 1973, Biological reviews of the Cambridge Philosophical Society.

[22]  J. Nedergaard,et al.  DNA synthesis in mouse brown adipose tissue is under β-adrenergic control☆ , 1989 .

[23]  H. Sprecher,et al.  An analysis of partial reactions in the overall chain elongation of saturated and unsaturated fatty acids by rat liver microsomes. , 1977, The Journal of biological chemistry.

[24]  M. Ashwell,et al.  Control of white and brown adipose tissues by the autonomic nervous system , 1987, Proceedings of the Nutrition Society.

[25]  I. Cameron,et al.  CYTOLOGICAL RESPONSES OF BROWN FAT TISSUE IN COLD-EXPOSED RATS , 1964, The Journal of cell biology.

[26]  B. Cannon,et al.  Native UCP1 Displays Simple Competitive Kinetics between the Regulators Purine Nucleotides and Fatty Acids* , 2004, Journal of Biological Chemistry.

[27]  B. Cannon,et al.  Chapter 17 The uncoupling protein thermogenin and mitochondrial thermogenesis , 1992 .

[28]  X. J. Musacchia,et al.  Regulation of depressed metabolism and thermogenesis , 1976 .

[29]  M. Frydman,et al.  Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: the dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis. , 1979, Canadian journal of physiology and pharmacology.

[30]  P. Tvrdik,et al.  Role of a New Mammalian Gene Family in the Biosynthesis of Very Long Chain Fatty Acids and Sphingolipids , 2000, The Journal of cell biology.

[31]  J. Lupien,et al.  Metabolic relationships between lipolysis and respiration in rat brown adipocytes. The role of long chain fatty acids as regulators of mitochondrial respiration and feedback inhibitors of lipolysis. , 1981, The Journal of biological chemistry.

[32]  M. Kaghad,et al.  The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[33]  P. Hemon,et al.  Changes induced by cold adaptation in the brown adipose tissue from several species of rodents, with special reference to the mitochondrial components. , 1979, Canadian journal of biochemistry.

[34]  A. Kuroshima,et al.  Muscle and brown adipose tissue fatty acid profiles in cold-exposed rats. , 1987, The Japanese journal of physiology.

[35]  E. Newsholme,et al.  Effect of some hormones on the rate of the triacylglycerol/fatty-acid substrate cycle in adipose tissue of the mouse in vivo , 1983, Bioscience reports.

[36]  M. Metzker,et al.  A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy , 2001, Nature Genetics.

[37]  B. Cannon,et al.  Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  J. Dorado,et al.  Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. , 2000, The Biochemical journal.

[39]  L. Svennerholm,et al.  A procedure for the quantitative isolation of brain gangliosides. , 1980, Biochimica et biophysica acta.

[40]  D. Nugteren The enzymic chain elongation of fatty acids by rat-liver microsomes. , 1965, Biochimica et biophysica acta.

[41]  P. Tvrdik,et al.  Cig30, a Mouse Member of a Novel Membrane Protein Gene Family, Is Involved in the Recruitment of Brown Adipose Tissue* , 1997, The Journal of Biological Chemistry.