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Increased Lipolysis and Decreased Leptin Production by Human Omental as Compared With Subcutaneous Preadipocytes

  1. Vanessa van Harmelen1,
  2. Andrea Dicker1,
  3. Mikael Rydén1,
  4. Hans Hauner2,
  5. Fredrik Lönnqvist1,
  6. Erik Näslund3 and
  7. Peter Arner1
  1. 1Department of Medicine, Karolinska Institute and Center for Metabolism and Endocrinology, Huddinge University Hospital, Stockholm, Sweden
  2. 2Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany
  3. 3Division of Surgery, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden

    Abstract

    Site differences in adipose tissue function may have implications for insulin-resistant conditions. In mature adipose tissue, subcutaneous adipocytes have higher leptin secretion, similar tumor necrosis factor (TNF)-α secretion, and lower catecholamine-stimulated lipolysis as compared with omental adipocytes. In this study, lipolysis and leptin and TNF-α secretion were compared between human omental and subcutaneous preadipocytes. After 16 days of incubation in a minimal differentiation medium, leptin mRNA and secretion were found to be two to eight times higher in subcutaneous than omental preadipocytes (P < 0.05). On the other hand, norepinephrine-induced lipolysis was about two times higher in the omental than in the subcutaneous preadipocytes, whereas basal lipolysis did not differ between the two regions. TNF-α secretion was marginally but significantly higher in the omental than in the subcutaneous preadipocytes. Preadipocyte differentiation was equal in both regions and was augmented to the same extent by different thiazolidinediones (rosiglitazone, pioglitazone, or troglitazone) in the two depots. In the presence of rosiglitazone, leptin secretion remained about three times higher and norepinephrine-induced lipolysis about six times lower in subcutaneous as compared with omental preadipocytes (P < 0.05), whereas TNF-α secretion and basal lipolysis were similar in preadipocytes from the two regions. These findings remained unaltered even if rosiglitazone was removed from the medium. However, leptin mRNA showed no regional differences in rosiglitazone-treated cells. Thus, regional differences in adipocyte leptin secretion as well as in norepinephrine-induced lipolysis are marked and present during different stages of preadipocyte differentiation and seem to be determined by intrinsic (i.e., primary) factors.

    Footnotes

    • Address correspondence and reprint requests to Peter Arner, Center for Metabolism and Endocrinology, MK Division, M63, Huddinge University Hospital, S-141 86 Huddinge, Sweden. E-mail: peter.arner{at}medhs.ki.se.

      Received for publication 25 October 2000 and accepted in revised form 17 December 2001.

      V.v.H and A.D. contributed equally to this study.

      DMEM, Dulbecco’s modified Eagle’s medium; ELISA, enzyme-linked immunosorbent assay; GPDH, glycerol-3-phosphate dehydrogenase; PPAR, peroxisome proliferator–activator receptor; TNF, tumor necrosis factor; TZD, thiazolidinedione.

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