1641-P: Changes in Adipocyte Function in Response to Weight Gain in Young, Lean European and South Asian Men

South Asians (SA) develop T2DM at younger age and lower BMI than Europeans (EU). We hypothesized that a low ability of pre-adipocytes to differentiate to adipocytes resulting in hypertrophy may explain the high risk of T2DM. Abdominal subcutaneous adipose tissue was obtained at baseline (BL) and after 6.3[SD1.3] % weight gain (WG) from 20 EU and 13 SA. Adipocytes and pre-adipocytes were isolated and adipocyte diameter measured. Gene expression was quantified relative to PPIA by rtPCR after pre-amplification and analysed using a mixed model. Diameter increased after WG in EU (BL 71[8] vs. WG 76[10] µm p=0.007, paired t test) but not in SA (85[12] vs. 86[11] µm p=0.40). SA had more large (L 90-145μm) and very large (VL >145μm) adipocytes than EU at BL (L 37.3 vs. 16.7%, VL 1.92 vs. 0.25 % p<0.001, χ² test) and after WG (41.1 vs. 23.1 %, 1.85 vs. 0.17 % p<0.001). Proportions of small (S <45µm) and L (S 10.0 vs. 4.7 %, L 16.7 vs. 23.1 % p<0.001) adipocytes were reduced and increased respectively in EU after WG. Smaller changes were seen in SA (S 6.2 vs. 4.1 %; L 37.3 vs. 41.0 % p=0.001). At BL and WG TNF expression was higher in SA (EU 0.04[0.04] vs. SA 0.12[0.15] % expression/PPIA p=0.004) while ADIPOQ (1069[372.1] vs. 874.1[271.8] % p=0.042) and ESR1 (6.7[3.0] vs. 4.2[2.8] % p<0.001) were lower. SREBF1 and LEP expressin were higher in SA and increased after WG, while INSR, SIRT1, CIDEA, GHR and PLIN2 were lower in SA and reduced after WG. An interaction (p=0.06) was found between ethnicity and WG for APOE which decreased after WG to a greater extent in EU (EU 42.2 vs. SA 16.6 % change in expression p<0.001). To conclude, SA store fat in larger adipocytes than EU that are minimally altered by WG. SA adipocytes express higher levels of inflammation and fat storage genes and lower levels of insulin sensitivity and adipogenesis genes which are further increased and decreased respectively by WG. The adverse impact of WG on SA adipocyte may underlie their higher risk of T2DM. Assessment of pre-adipocyte differentiation ability in response to WG is underway.