LIPID LABORATORY, KAROLINSKA INSTITUTE AT HUDDINGE HOSPITAL

1. The importance of hormone-sensitive lipase for lipolytic capacity in human fat cells is investigated together with the Toulouse group (D. Langin). In particular we are interested in the relationship between the expression in human fat cells of the short and long forms, respectively of the lipase, on the one side and lipolytic capacity on the other side.

2. In collaboration with the Oxford group (K. Frayn) a project has been started to study the regulation of blood flow in human adipose tissue. A special device is constructed by which vasoactive drugs can be infused locally in the subcutaneous adipose tissue and tissue flow being measured by the Xenon-washout technique. The previous knowledge about blood flow regulation as measured by microdialysis at the Lipid Laboratory will form the basis of the design of studies.

3. A project to characterize catecholamine-induced lipolysis in vivo in human skeletal muscle has just started in collaboration with the Maastricht group (E Blaak). In this project whole body lipolysis will also be evaluated by a stable isotope technique (glycerol).

4. The importance of gene polymorphism in the lipolytic beta-adrenoceptor pathway will be investigated in collaboration with the Maastricht group (E Blaak). In Maastricht a large number of obese subjects have been investigated regarding isoprenaline stimulated lipolysis in vivo. Isoprenaline is a non-selective beta-adrenergic agonist. DNA from the subjects has been collected. At Lipid Laboratory, we will genotype for all known functional polymorphisms in the beta1- and beta2-adrenoceptors as well as in the G-beta3 component of the coupling G protein.

References

  1. V Van Harmelen, S Reynisdottir, K Cianflone, E Degerman, J Hoffstedt, K Nilsell, A Sniderman, P Arner. Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin. J Biol Chem 274: 18243-18251, 1999.

  2. H Wahrenberg, I Ek, S Reynisdottir, K Carlstrom, A Bergqvist, P Arner. Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 84: 2182-2187, 1999.

  3. V Large, S Reynisdottir, D Langin, K Fredby, M Klannemark, C Holm, P Arner. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40: 2059-2065, 1999

  4. K Andersson, N Gaudiot, C Ribiere, M Elizalde, Y Giudicelli, P Arner. A nitric oxide-mediated mechanism regulates lipolysis in human adipose tissue in vivo. Br J Pharmacol 126: 16391645, 1999.

  5. J Hoffstedt, P Eriksson, L Hellstrom, S Rössner, M Ryden, P Arner. Excessive fat accumulation is associated with the TNFalpha-308 G/A promoter polymo120,rphism in women but not in men. Diabetologia 43: 117- 2000.
  6. P Lofgren, V Van Harmelen, S Reynisdottir, E Näslund, M Ryden, S Rossner, P Arner. Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue. Diabetes 49: 688-692, 2000.
  7. J Bolinder, DAJM Kerckhoffs, E Moberg, E Hagstrom-Toft, P Arner. Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects. Diabetes 49: 797-802, 2000.
  8. M Elizalde, M Ryden, V Van Harmelen, P Eneroth, H Gyllenhammar, C Holm, S Ramel, A Olund, P Arner, K Andersson. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res 41: 1244-1251, 2000.