Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

Journal Article · Mon Aug 15 04:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.05.003· OSTI ID:20717647

Grohmann, Malcolm ^[1]; Stewart, Claire ^[2]; Welsh, Gavin ^[3]; Hunt, Linda ^[4]; Tavare, Jeremy ^[3]; Holly, Jeff ^[1]; Shield, Julian ^[4]; Sabin, Matt ^[4]; Crowne, Elizabeth ^[4]

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1. Department of Surgery, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol (United Kingdom)
2. Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager (United Kingdom)
3. Department of Biochemistry, University of Bristol, University Walk, Bristol (United Kingdom)
4. Department of Paediatric Endocrinology, Institute of Child Health, University of Bristol, Royal Hospital for Children, Upper Maudlin Street, Bristol (United Kingdom)

Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNF{alpha} exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNF{alpha} (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNF{alpha} also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNF{alpha} exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation.

• OSTI ID: 20717647
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 308; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
CATTLE
CHEMILUMINESCENCE
EDTA
FAT CELLS
GELS
GLUCOSE
GLYCOGEN
INSULIN
METABOLIC DISEASES
PHOSPHATES
PHOSPHORYLATION
RECEPTORS
TRITIUM