IGFBP-2 inhibits lipogenesis in visceral, but not subcutaneous, adipocytes — ASN Events
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  3. IGFBP-2 inhibits lipogenesis in visceral, but not subcutaneous, adipocytes

IGFBP-2 inhibits lipogenesis in visceral, but not subcutaneous, adipocytes (#29)

Steven W Yau 1 2 3 , Vincenzo C Russo 1 2 , Iain J Clarke 3 , George A Werther 1 2 , Matthew A Sabin 1 2 3
  1. Centre for Hormone Research, Murdoch Childrens Research Institute, Parkville, VIC, Australia
  2. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
  3. Department of Physiology, Monash University, Clayton, VIC, Australia

Introduction: Subcutaneous and visceral adipocytes have molecular and functional differences, with increased visceral adiposity contributing to the development of the metabolic syndrome1. Insulin-like growth factor binding protein-2 (IGFBP-2) is the principal IGFBP produced by white adipocytes during adipogenesis2 and circulating levels are reduced in obese adults3 and children4. Transgenic mice whose adipocytes overexpress IGFBP-2 do not develop obesity, even when overfed5, however the depot-specific effects of IGFBP-2 on lipogenesis have not been explored.

Aims: To investigate whether IGFBP-2 differentially affects lipogenesis in visceral and subcutaneous adipocytes.

Methods: Treatments in human subcutaneous and visceral preadipocytes cultures (differentiated without exogenous IGF-I) were as follows: A) Preadipocytes differentiated for 10 days with conditioned media collected daily for quantification of IGFBP-2 (ELISA). B) Preadipocytes treated with IGFBP-2 (100ng/ml) at days 0 and 7 of differentiation until day 8. C) Differentiated adipocytes treated with IGFBP-2 for 24h. D) Differentiated adipocytes treated with IGFBP-2 siRNA for 24h followed by ‘add-back’ of IGFBP-2 (24h). Outcomes included gene expression of phosphoenolpyruvate carboxykinase (PEPCK), Sterol Regulatory Element Binding Protein-1c (SREBP1c) and Fatty Acid Synthase (FAS) by qPCR and lipid staining (LipidTOX neutral red).

Results: A) During differentiation, visceral preadipocytes secreted more (p<0.001) IGFBP-2 than subcutaneous preadipocytes. B) IGFBP-2 reduced lipid staining by 70% (p<0.001) and 28% (p<0.05) on days 0 and 7 respectively in visceral adipocytes (no effect in subcutaneous adipocytes). C) IGFBP-2 reduced PEPCK, SREBP1c and FAS expression (p<0.001) in visceral adipocytes only. D) Silencing IGFBP-2 increased PEPCK, SREBP1c and FAS mRNA expression (p<0.05) and enhanced lipid staining (p<0.01) in visceral adipocytes only. Add-back IGFBP-2 restored SREBP1c and FAS mRNA expression (p<0.01), and restored lipid staining (p<0.05) changes seen in visceral adipocytes.

Conclusion: IGFBP-2 inhibits markers of lipogenesis in visceral, but not subcutaneous, adipocytes- indicating a depot-specific impairment of adipocyte differentiation. IGFBP-2 may be a novel target for obesity prevention.

  1. Ibrahim, M.M Subcutaneous and visceral adipose tissue: structural and functional differences. Obesity Rev 2010;11:11-18.
  2. Boney, CM et al. Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins during adipogenesis. Endocrinology 1994;135:1863-8.
  3. Nam, SY et al. Effect of obesity on total and free insulin-like growth factor (IGF)-I, and their relationship of IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord 1997;21:355-9.
  4. Claudio, M et al. Adipocytes IGFBP-2 expression in prepubertal obese children. Obesity (Silver Spring) 2010;18:2055-7.
  5. Wheatcroft, SB et al. IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes 2007;56:285-94.
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